Descriptor: "MESH : B-Lymphocytes" - Searchworks@Jio Institute Digital Library Search Results

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29 results on '"MESH : B-Lymphocytes"'

1. Candida albicans is able to use M cells as a portal of entry across the intestinal barrier in vitro

Author: Albac, Sandrine, Schmitz, Antonin, Lopez-Alayon, Carolina, d'Enfert, Christophe, Sautour, Marc, Ducreux, Amandine, Labruère-Chazal, Catherine, Laue, Michael, Holland, Gudrun, Bonnin, Alain, Dalle, Frederic, Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Biologie et Pathogénicité fongiques, Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Laboratoire de parasitologie mycologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Mathématiques de Bourgogne [Dijon] (IMB), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB), Robert Koch Institute [Berlin] (RKI), Agence Nationale de la Recherche. Grant Number: ANR-08-MIEN- 033-01 BIOASTER-Sanofi-Alliance pour les Sciences de la Vie et de la Santé (AVIESAN) Investissement d'Avenir. Grant Number: ANR-10-AIRT-03, ANR-08-MIEN-0033,KANJI,Colonisation et invasion de la muqueuse digestive par le champignon pathogène de l'homme Candida albicans(2008), ANR-10-AIRT-0005,NANOELEC,NANOELEC(2010), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), ANR: ANR-10-AIRT-05,Programme Investissements d’Avenir, Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut National de la Recherche Agronomique ( INRA ) -Institut Pasteur [Paris], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de Mathématiques de Bourgogne [Dijon] ( IMB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Robert Koch Institute [Berlin] ( RKI ), ANR-08-MIEN-0033,KANJI,Colonisation et invasion de la muqueuse digestive par le champignon pathogène de l'homme Candida albicans ( 2008 ), ANR : ANR-10-AIRT-05,Programme Investissements d’Avenir, Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), and Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Cell Line, MESH : Coculture Techniques, MESH : Microscopy, Fluorescence, [SDV]Life Sciences [q-bio], MESH: Microscopy, Fluorescence, MESH: Candidemia, Peyer's Patches, Mucosal immunity, Invasion, Candida albicans, MESH : Host-Pathogen Interactions, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, B-Lymphocytes, Endocytosis, MESH : Epithelial Cells, MESH : Peyer's Patches, MESH: Epithelial Cells, Host-Pathogen Interactions, MESH: Endocytosis, Adhesion, Transcytosis, Infection, MESH : Microscopy, Electron, Scanning, MESH : Candida albicans, MESH: Microscopy, Electron, Scanning, MESH : Endocytosis, MESH : B-Lymphocytes, Cell Line, MESH: Cell Adhesion, MESH: Coculture Techniques, MESH: B-Lymphocytes, Cell Adhesion, MESH : Candidemia, Humans, MESH: Humans, [ SDV ] Life Sciences [q-bio], MESH: Candida albicans, MESH : Humans, MESH: Host-Pathogen Interactions, Candidemia, Epithelial Cells, Coculture Techniques, MESH: Cell Line, Gastrointestinal Tract, MESH : Cell Adhesion, Microscopy, Fluorescence, Microscopy, Electron, Scanning, MESH: Peyer's Patches, MESH: Gastrointestinal Tract, MESH : Gastrointestinal Tract
Abstract: International audience; Candida albicans is the most frequent yeast responsible for systemic infections in humans. These infections mainly originate from the gastrointestinal tract where C. albicans can invade the gut epithelial barrier to gain access to the bloodstream. Along the gut, pathogens can use Microfold (M) cells as a portal of entry to cross the epithelial barrier. M cells are specialized cells mainly located in the follicule-associated epithelium of Peyer patches. In this study, we used scanning electron and fluorescence microscopy, adhesion and invasion assays and fungal mutants to investigate the interactions of C. albicans with M cells obtained in an established in vitro model whereby enterocyte-like Caco-2 cells co-cultured with the Raji B cell line undergo a phenotypic switch to morphologically and functionally resembling M cells. Our data demonstrate that C. albicans co-localizes with and invades preferentially M cells, providing evidence that the fungus can use M cells as a portal of entry into the intestinal barrier. In addition to active penetration, F-actin dependent endocytosis contributes to internalization of the fungus into M cells through a mechanism involving hypha-associated invasins including Ssa1 and Als3.
Published: 2016
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2. Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor

Author: Marc Stern, Marie-Hélène Delfau-Larue, Hervé Mal, Diane Damotte, Magali Colombat, Michel Fournier, Patrice Callard, Jacques Diebold, Jean-Pierre Farcet, Christiane Copie-Bergman, Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service de pneumologie B, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Service d'anatomie pathologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service d'immunologie biologique, Service de pneumologie, and Hôpital Foch [Suresnes]
Subjects: Lung Diseases, Pathology, MESH : Molecular Sequence Data, MESH : DNA, medicine.medical_treatment, Immunoglobulin Variable Region, Paraproteinemias, MESH : Immunoglobulin Heavy Chains, Plasma cell, Biochemistry, 0302 clinical medicine, MESH : Female, MESH : Immunoglobulin Variable Region, B-Lymphocytes, 0303 health sciences, MESH : Lung Diseases, Cysts, MESH : Amino Acid Sequence, Hematology, MESH : Adult, MESH : Immunoglobulin Light Chains, 3. Good health, medicine.anatomical_structure, MESH : Paraproteinemias, 030220 oncology & carcinogenesis, MESH : Lung Transplantation, Female, Genes, Immunoglobulin Light Chain, Immunoglobulin Heavy Chains, Lung Transplantation, Adult, medicine.medical_specialty, Genes, Immunoglobulin Heavy Chain, Molecular Sequence Data, Immunology, MESH : Genes, Immunoglobulin Heavy Chain, MESH : Cysts, Biology, Immunoglobulin light chain, Article, Light chain deposition disease, MESH : B-Lymphocytes, Lung Disorder, Immunoglobulin kappa-Chains, 03 medical and health sciences, MESH : Immunoglobulin kappa-Chains, medicine, Humans, Lung transplantation, Amino Acid Sequence, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Genes, Immunoglobulin Light Chain, 030304 developmental biology, Lung, Base Sequence, MESH : Humans, DNA, Cell Biology, medicine.disease, Immunoglobulin heavy chain, MESH : Base Sequence, Immunoglobulin Light Chains, CD5
Abstract: We have recently described a new form of light chain deposition disease (LCDD) presenting as a severe cystic lung disorder requiring lung transplantation. There was no bone marrow plasma cell proliferation. Because of the absence of disease recurrence after bilateral lung transplantation and of serum-free light chain ratio normalization after the procedure, we hypothesized that monoclonal light chain synthesis occurred within the lung. The aim of this study was to look for the monoclonal B-cell component in 3 patients with cystic lung LCDD. Histologic examination of the explanted lungs showed diffuse nonamyloid κ light chain deposits associated with a mild lymphoid infiltrate composed of aggregates of small CD20+, CD5−, CD10− B lymphocytes reminiscent of bronchus-associated lymphoid tissue. Using polymerase chain reaction (PCR), we identified a dominant B-cell clone in the lung in the 3 studied patients. The clonal expansion of each patient shared an unmutated antigen receptor variable region sequence characterized by the use of IGHV4-34 and IGKV1 subgroups with heavy and light chain CDR3 sequences of more than 80% amino acid identity, a feature evocative of an antigen-driven process. Combined with clinical and biologic data, our results strongly argue for a new antigen-driven primary pulmonary lymphoproliferative disorder.
Published: 2008
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3. CD40 Ligand Protects from TRAIL-Induced Apoptosis in Follicular Lymphomas through NF-κB Activation and Up-Regulation of c-FLIP and Bcl-xL

Author: Patricia Amé-Thomas, Thierry Lamy, Olivier Micheau, Alexandre Morizot, Marion Travert, G. Semana, Thierry Guillaudeux, Céline Pangault, Thierry Fest, Karin Tarte, Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Hématologie, Immunologie et de Thérapie Cellulaire ( HITC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Le Corre, Morgane
Subjects: CD4-Positive T-Lymphocytes, MESH: Signal Transduction, MESH: CASP8 and FADD-Like Apoptosis Regulating Protein, Palatine Tonsil, CASP8 and FADD-Like Apoptosis Regulating Protein, MESH: NF-kappa B, Apoptosis, MESH: Caspase 8, Receptors, Tumor Necrosis Factor, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, TNF-Related Apoptosis-Inducing Ligand, MESH: Recombinant Proteins, MESH : TNF-Related Apoptosis-Inducing Ligand, MESH: Lymphoma, Follicular, 0302 clinical medicine, MESH: Up-Regulation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Cytotoxic T cell, MESH : Nitriles, Sulfones, MESH : Antigens, CD40, Lymphoma, Follicular, MESH : Up-Regulation, Cells, Cultured, B-Lymphocytes, Caspase 8, 0303 health sciences, MESH : Caspase 8, biology, NF-kappa B, MESH: CD4-Positive T-Lymphocytes, MESH: Sulfones, Recombinant Proteins, MESH: Nitriles, Up-Regulation, Cell biology, medicine.anatomical_structure, MESH : CD4-Positive T-Lymphocytes, MESH : NF-kappa B, 030220 oncology & carcinogenesis, MESH: Palatine Tonsil, [SDV.IMM]Life Sciences [q-bio]/Immunology, Signal transduction, MESH: TNF-Related Apoptosis-Inducing Ligand, Signal Transduction, MESH: Cells, Cultured, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Recombinant Proteins, T cell, CD40 Ligand, Immunology, bcl-X Protein, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bcl-xL, MESH: Antigens, CD40, MESH: bcl-X Protein, MESH : B-Lymphocytes, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, MESH: B-Lymphocytes, Nitriles, MESH : Cells, Cultured, medicine, Humans, CD40 Antigens, MESH: Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Sulfones, MESH : Palatine Tonsil, MESH: CD40 Ligand, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, CD40, MESH : Cell Line, Tumor, MESH: Apoptosis, MESH : bcl-X Protein, MESH : Lymphoma, Follicular, MESH : Humans, Germinal center, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, MESH: Receptors, Tumor Necrosis Factor, MESH : CD40 Ligand, MESH : Receptors, Tumor Necrosis Factor, Receptors, TNF-Related Apoptosis-Inducing Ligand, biology.protein, MESH : Apoptosis
Abstract: The TNF family member TRAIL is emerging as a promising cytotoxic molecule for antitumor therapy. However, its mechanism of action and the possible modulation of its effect by the microenvironment in follicular lymphomas (FL) remain unknown. We show here that TRAIL is cytotoxic only against FL B cells and not against normal B cells, and that DR4 is the main receptor involved in the initiation of the apoptotic cascade. However, the engagement of CD40 by its ligand, mainly expressed on a specific germinal center CD4+ T cell subpopulation, counteracts TRAIL-induced apoptosis in FL B cells. CD40 induces a rapid RNA and protein up-regulation of c-FLIP and Bcl-xL. The induction of these antiapoptotic molecules as well as the inhibition of TRAIL-induced apoptosis by CD40 is partially abolished when NF-κB activity is inhibited by a selective inhibitor, BAY 117085. Thus, the antiapoptotic signaling of CD40, which interferes with TRAIL-induced apoptosis in FL B cells, involves NF-κB-mediated induction of c-FLIP and Bcl-xL which can respectively interfere with caspase 8 activation or mitochondrial-mediated apoptosis. These findings suggest that a cotreatment with TRAIL and an inhibitor of NF-κB signaling or a blocking anti-CD40 Ab could be of great interest in FL therapy.
Published: 2008
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4. The human spleen is a major reservoir for long-lived vaccinia virus–specific memory B cells

Author: Jean-Claude Weill, Bertrand Godeau, François Paye, Nina Arakelyan, Alain Sauvanet, Pierre Buffet, Odile Beyne-Rauzy, Bruno Varet, Sandra K. Weller, Anne Berger, Jacques-Olivier Pers, Maria Mamani-Matsuda, Claude-Agnès Reynaud, Claire Fieschi, Caroline Staib, Loïc Garçon, Marc Michel, Ahmad Faili, Olivier Hermine, Antonio Cosma, Jean-Marie Andrieu, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Clinical cooperation group 'Immune monitoring', German Research Center for Environmental Health - Helmholtz Center München (GmbH), Clinical cooperation group 'Antigen-specific immunotherapy', Institute of Molecular Virology, Institute of Virology, Technical University, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne et Immunopathologie, CHU Toulouse [Toulouse], Laboratoire d'immunologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service de Chirurgie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Beaujon, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Médical de l'Institut Pasteur, Institut Pasteur [Paris], This work was supported by the Fondation Princesse Grace, the Agence Nationale pour la Recherche ('B cell memory', MIIM program) and the Ligue Contre le Cancer (Equipe labellisée). M.M.-M. was supported by successive fellowships from the Fondation de France, the Fondation Singer-Polignac and the Région Ile-de- France, and ANR : 'B cell memory', MIIM program,'B cell memory', MIIM program
Subjects: MESH : Spleen, MESH : Case-Control Studies, MESH : Immunoglobulin G, MESH : Immunologic Memory, Immunology, Naive B cell, Vaccinia virus, Spleen, Biochemistry, Immunoglobulin G, Virus, MESH : B-Lymphocytes, 03 medical and health sciences, 0302 clinical medicine, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, MESH : Splenectomy, 030304 developmental biology, B-Lymphocytes, 0303 health sciences, MESH : Vaccinia virus, biology, MESH : Humans, Cell Biology, Hematology, Virology, 3. Good health, B-1 cell, medicine.anatomical_structure, Case-Control Studies, Splenectomy, biology.protein, Antibody, Million Cells, Immunologic Memory, Homeostasis, 030215 immunology
Abstract: The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We report that, whereas blood and spleen compartments present similar frequencies of IgG+ cells, antismallpox memory B cells are specifically enriched in the spleen where they account for 0.24% of all IgG+ cells (ie, 10-20 million cells) more than 30 years after vaccination. They represent, in contrast, only 0.07% of circulating IgG+ B cells in blood (ie, 50-100 000 cells). An analysis of patients either splenectomized or rituximab-treated confirmed that the spleen is a major reservoir for long-lived memory B cells. No significant correlation was observed between the abundance of these cells in blood and serum titers of antivaccinia virus antibodies in this study, including in the contrasted cases of B cell– depleting treatments. Altogether, these data provide evidence that in humans, the two arms of B-cell memory—long-lived memory B cells and plasma cells—have specific anatomic distributions—spleen and bone marrow—and homeostatic regulation.
Published: 2008
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5. DNA polymerases in adaptive immunity. : DNA polymerases in adaptive immunity

Author: Claude-Agnès Reynaud, Jean-Claude Weill, Développement du Systeme Immunitaire, and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: History, MESH : DNA-Directed DNA Polymerase, DNA polymerase, Gene Conversion, MESH : Somatic Hypermutation, Immunoglobulin, DNA-Directed DNA Polymerase, Computational biology, diversity, MESH : B-Lymphocytes, Education, chemistry.chemical_compound, Immune system, Animals, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Immunoglobulin Class Switching, Polymerase, Genetics, B-Lymphocytes, MESH : Gene Conversion, biology, Immunoglobulin genes, MESH : Immunity, Active, MESH : Humans, repertoire, Acquired immune system, Immunoglobulin Class Switching, Computer Science Applications, polymerase, Immunity, Active, chemistry, immunoglobulin genes, biology.protein, Somatic Hypermutation, Immunoglobulin, MESH : Animals, DNA
Abstract: review article; International audience; To cope with an unpredictable variety of potential pathogenic insults, the immune system must generate an enormous diversity of recognition structures, and it does so by making stepwise modifications at key genetic loci in each lymphoid cell. These modifications proceed through the action of lymphoid-specific proteins acting together with the general DNA-repair machinery of the cell. Strikingly, these general mechanisms are usually diverted from their normal functions, being used in rather atypical ways in order to privilege diversity over accuracy. In this Review, we focus on the contribution of a set of DNA polymerases discovered in the past decade to these unique DNA transactions.
Published: 2008
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6. Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+IgD+CD27+ B cell repertoire in infants

Author: Maria Mamani-Matsuda, Frédéric Gauthier, Claude-Agnès Reynaud, Corinne Cordier, Capucine Picard, Damiana Lecoeuche, Jean-Claude Weill, Sandra K. Weller, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Ligue Nationale contre le Cancer, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, and Weller, Sandra
Subjects: MESH: Spleen, MESH: Antigens, CD27, MESH: Immunoglobulin Variable Region, Immunoglobulin D, MESH: Variation (Genetics), 0302 clinical medicine, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Immunoglobulin Variable Region, MESH: Antigens, CD, 0303 health sciences, biology, MESH : Variation (Genetics), MESH: Immunoglobulin D, MESH : Infant, hemic and immune systems, Articles, MESH: Infant, MESH: Immunoglobulin M, somatic hypermutation, "somatic hypermutation", MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: B-Lymphocyte Subsets, MESH : Spleen, MESH: Immunoglobulin mu-Chains, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Immunologic Memory, MESH: Gene Rearrangement, MESH : Immunoglobulin M, Immunology, Somatic hypermutation, "splenic marginal zone", chemical and pharmacologic phenomena, MESH : Immunoglobulin D, Article, MESH : B-Lymphocytes, 03 medical and health sciences, Immune system, Antigen, MESH : Antigens, CD27, MESH: B-Lymphocytes, MESH : Antigens, CD, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, MESH : T-Lymphocytes, MESH: Humans, MESH: Transcription, Genetic, MESH : Humans, Ig repertoire, Germinal center, MESH : Transcription, Genetic, Gene rearrangement, MESH : Gene Rearrangement, splenic marginal zone, B-1 cell, MESH: T-Lymphocytes, MESH : Immunoglobulin mu-Chains, Immunoglobulin M, biology.protein, 030215 immunology, MESH : B-Lymphocyte Subsets, "Ig repertoire"
Abstract: International audience; T cell-dependent immune responses develop soon after birth, whereas it takes 2 yr for humans to develop T cell-independent responses. We used this dissociation to analyze the repertoire diversification of IgM(+)IgD(+)CD27(+) B cells (also known as "IgM memory" B cells), comparing these cells with switched B cells in children
Published: 2008
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7. Quantitative analysis of inflammatory cells infiltrating the cystic fibrosis airway mucosa

Author: C. Hubeau, J. P. Couetil, D. Hubert, Dominique Gaillard, E. Puchelle, D. Dusser, M. Lorenzato, Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'histologie, cytologie, biologie cellulaire et moléculaire Pol Bouin, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Birembaut, Philippe, Université de Reims Champagne-Ardenne ( URCA ) -IFR53-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Reims Champagne-Ardenne ( URCA ) -Centre Hospitalier Universitaire de Reims ( CHU Reims ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]
Subjects: Male, MESH: Inflammation, MESH: Bronchiectasis, Pathology, MESH: Macrophages, Alveolar, Cystic Fibrosis, Lymphocyte, Cell Count, MESH : Cell Count, CD38, Lung Disease, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Epithelium, 0302 clinical medicine, T-Lymphocyte Subsets, Immunology and Allergy, MESH : Female, Mast Cells, Lung, Respiratory Tract Infections, MESH : E-Selectin, B-Lymphocytes, 0303 health sciences, MESH: Bronchi, MESH: Mast Cells, MESH : Adult, respiratory system, Intercellular Adhesion Molecule-1, MESH : Bronchi, Bronchiectasis, 3. Good health, medicine.anatomical_structure, Neutrophil Infiltration, MESH : Macrophages, Alveolar, MESH : Lung Transplantation, Female, MESH : Mast Cells, medicine.symptom, E-Selectin, Lung Transplantation, Adult, MESH: E-Selectin, medicine.medical_specialty, MESH: Cystic Fibrosis, MESH : Lung, MESH : Male, Plasma Cells, Immunology, Vascular Cell Adhesion Molecule-1, Bronchi, Inflammation, Biology, MESH : B-Lymphocytes, 03 medical and health sciences, Immune system, MESH : Bronchiectasis, MESH : Cystic Fibrosis, MESH: B-Lymphocytes, Macrophages, Alveolar, medicine, Humans, MESH: Lung, MESH : M, 030304 developmental biology, Bronchus, Mucous Membrane, MESH : Inflammation, MESH: Humans, MESH : Intercellular Adhesion Molecule-1, MESH: Cell Count, MESH: Intercellular Adhesion Molecule-1, MESH : Humans, MESH: Biological Markers, MESH: Adult, MESH : Epithelium, MESH: Male, MESH : Biological Markers, Transplantation, MESH: Epithelium, MESH: M, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Lung Transplantation, MESH: Female, Biomarkers, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, CD8
Abstract: SUMMARYAirway inflammation represents a hallmark of the cystic fibrosis (CF) disease. However, the mucosal distribution of immune cells along the CF airways has not been clearly defined, particularly in intermediate bronchi and distal bronchioles. We analysed lung tissues collected at the time of transplantation from homozygous ΔF508+/+CF patients versus non-CF donors. Using immunohistochemistry, the distribution of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, polymorphonuclear neutrophils (PMN), mast cells, CD3+ T cells, including the CD4+ and CD8+ subsets, CD20+ B cells, CD38+ plasma cells and CD68+ macrophages, was analysed at lobar, segmental and distal levels of the bronchial tree. Using image cytometry, the number of cells per mm2 was assessed in the depth of the bronchial wall. In CF airways, alterations mainly consisted in lesions of the surface epithelium. Numerous immune cells were heterogeneously distributed all along the bronchial tree and mainly located in the mucosa, beneath the surface epithelium. Compared to non-CF donors, the lymphoid aggregates formed by B cells were significantly larger all along the CF airways (P = 0·001). The number of T lymphocytes was higher at the CF distal level (P = 0·035), where we observed an intense tissue damage. PMN preferentially accumulated (P = 0·033) in the CF surface epithelium, which overexpressed ICAM-1 but not VCAM-1 and E-selectin. These results highlight the nature of the inflammatory infiltrate in the CF airway mucosa and emphasize a prominent implication of PMN, B and T lymphocytes in the CF disease.
Published: 2001
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8. Persistence of natural killer cells with expansion of a hypofunctional CD56-CD16+KIR+NKG2C+ subset in a patient with atypical Janus kinase 3-deficient severe combined immunodeficiency

Author: Capucine Picard, Florence Orlanducci, Catherine Farnarier, Daniel Olive, Geneviève de Saint Basile, Alain Fischer, Laure Farnault, Hervé Chambost, Alessandro Moretta, Christophe Picard, Gérard Michel, Isabelle Thuret, Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Dipartimento di Medicina Sperimentale, Universita degli studi di Genova, Collège de France - Chaire Médecine expérimentale (A. Fischer), Università degli studi di Genova = University of Genoa (UniGe), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), and University of Genova
Subjects: MESH : Janus Kinase 3, Persistence (psychology), MESH: Killer Cells, Natural, MESH : Male, [SDV]Life Sciences [q-bio], Immunology, MESH : Severe Combined Immunodeficiency, MESH: Severe Combined Immunodeficiency, MESH : Child, Preschool, Biology, CD16, MESH: Receptors, IgG, MESH : B-Lymphocytes, MESH: Janus Kinase 3, 03 medical and health sciences, 0302 clinical medicine, MESH: Receptors, KIR, MESH: B-Lymphocytes, MESH : Consanguinity, medicine, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Immunology and Allergy, MESH : Receptors, IgG, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, MESH : T-Lymphocytes, MESH: Consanguinity, 0303 health sciences, Severe combined immunodeficiency, MESH: Humans, [ SDV ] Life Sciences [q-bio], Janus kinase 3, MESH : Humans, MESH: Child, Preschool, MESH : Receptors, KIR, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Antigens, CD56, medicine.disease, Virology, MESH: Male, MESH : NK Cell Lectin-Like Receptor Subfamily C, 3. Good health, MESH: NK Cell Lectin-Like Receptor Subfamily C, MESH: T-Lymphocytes, MESH : Antigens, CD56, MESH : Killer Cells, Natural, 030215 immunology
Abstract: International audience
Published: 2013
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9. Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort

Author: Pascale Roux-Lombard, Alain Cantagrel, Xavier Mariette, Gilles Chiocchia, Jacques-Eric Gottenberg, Beatrice Ducot, Cédric Lukas, Alain Saraux, Jean-Michel Dayer, Service de rhumatologie, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Division of Immunology and Allergy, University Hospital, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Rhumatologie ( Toulouse - Rhumato ), CHU Toulouse [Toulouse], Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre d'Investigation Clinique ( CIC - Brest ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Immunologie et d'Allergologie ( SIA - GENEVE ), Hôpitaux Universitaires de Genève ( HUG ), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Rhumatologie (Toulouse - Rhumato), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Immunologie et d'Allergologie (SIA - GENEVE), Hôpitaux Universitaires de Genève (HUG), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre
Subjects: Male, MESH : Prospective Studies, Arthritis, Lymphocyte Activation, MESH : Early Diagnosis, Arthritis, Rheumatoid, 0302 clinical medicine, MESH: Early Diagnosis, Outcome Assessment, Health Care, Immunology and Allergy, MESH : Female, Prospective Studies, Biological Markers/blood, MESH : Joints, ddc:616, 0303 health sciences, B-Lymphocytes, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, biology, medicine.diagnostic_test, Interleukin, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Adult, Middle Aged, Connective tissue disease, 3. Good health, MESH: Joints, Hyperalgesia, Rheumatoid arthritis, Erythrocyte sedimentation rate, Female, Adult, medicine.medical_specialty, MESH: Interleukins, MESH : Outcome Assessment (Health Care), MESH : Interleukin-6, MESH : Male, Immunology, General Biochemistry, Genetics and Molecular Biology, MESH : B-Lymphocytes, 03 medical and health sciences, Outcome Assessment (Health Care), Rheumatology, Internal medicine, MESH: B-Lymphocytes, medicine, MESH : Hyperalgesia, Hyperalgesia/pathology/physiopathology, Rheumatoid factor, Humans, MESH : Middle Aged, Joints/pathology/physiopathology, Arthritis, Rheumatoid/blood/diagnosis/immunology, Interleukin 6, MESH: Lymphocyte Activation, MESH: Outcome Assessment (Health Care), MESH : Lymphocyte Activation, 030304 developmental biology, B-Lymphocytes/immunology/metabolism/pathology, 030203 arthritis & rheumatology, MESH: Humans, business.industry, Interleukin-6, Interleukins, MESH : Humans, MESH: Biological Markers, MESH: Adult, Interleukins/blood, medicine.disease, MESH: Hyperalgesia, MESH: Interleukin-6, MESH: Male, MESH: Prospective Studies, MESH : Biological Markers, Early Diagnosis, MESH : Arthritis, Rheumatoid, biology.protein, Joints, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Interleukin-6/blood, business, MESH : Interleukins, MESH: Female, Biomarkers
Abstract: International audience; OBJECTIVE: To identify a specific pattern of serum cytokines that correlates with the diagnosis, activity and severity of rheumatoid arthritis (RA) in patients with early RA as well as with the level of serum markers of B cell activation. METHODS: Serum interleukin (IL)-1β, IL-1 receptor antagonist (IL1-Ra), IL-2, IL-4, IL-6, IL-10, IL-17, IL-21, monocyte chemotactic protein 1 (MCP-1), tumour necrosis factor α and interferon γ levels were measured in the (ESPOIR) Etude et Suivi des POlyarthrites Indifférenciées Récentes early arthritis cohort, which included patients with at least two swollen joints for >6 weeks and
Published: 2012
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10. Multifocal polyclonal Epstein-Barr virus-associated B-cell lymphoproliferative disorder secondary to azathioprine therapy successfully treated with rituximab

Author: Philippe Gaulard, Dimitri Salameire, Virginie Hincky-Vitrat, Blandine Fabre, Stéphane Courby, Remy Gressin, Olivier Epaulard, Bruno Bonaz, Department of clinical hematology, CHU Grenoble, Department of pathology, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of infectious diseases, Différenciation et prolifération des cellules souches adultes. application à la thérapie cellulaire hématopoiétique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANTE-INSERM U836, équipe 8, Stress et interactions neurodigestives, Department of Gastroenterology, CHU Grenoble-CHU Grenoble, Université Joseph Fourier, Sinniger, Valérie, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: Cancer Research, Azathioprine, medicine.disease_cause, MESH: Antibodies, Monoclonal, MESH: Lung Diseases, 0302 clinical medicine, MESH: Lymphoproliferative Disorders, MESH : Azathioprine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, hemic and lymphatic diseases, MESH : Tomography, X-Ray Computed, MESH : Female, MESH : Immunosuppressive Agents, MESH: Treatment Outcome, 0303 health sciences, biology, MESH : Lymphoproliferative Disorders, MESH : Lung Diseases, Azathioprine therapy, Hematology, MESH : Adult, MESH : Herpesvirus 4, Human, 3. Good health, MESH : Antineoplastic Agents, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine.anatomical_structure, Oncology, MESH : Antibodies, Monoclonal, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, Rituximab, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Immunosuppressive Agents, MESH: Tomography, X-Ray Computed, medicine.drug, MESH : Treatment Outcome, MESH : Crohn Disease, Virus, MESH : B-Lymphocytes, 03 medical and health sciences, MESH: B-Lymphocytes, medicine, B cell, MESH: Azathioprine, 030304 developmental biology, MESH: Humans, MESH: Crohn Disease, Crohn disease, business.industry, MESH : Humans, MESH: Adult, MESH: Herpesvirus 4, Human, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Epstein–Barr virus, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Polyclonal antibodies, Immunology, biology.protein, MESH: Antineoplastic Agents, business, MESH: Female
Abstract: We describe the case of a woman with Crohn disease treated with azathioprine (AZA) who developed a multisystemic Epstein–Barr virus (EBV)-related polyclonal B-cell lymphoproliferative disorder. A 3...
Published: 2010
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11. Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg cells and normal B-lymphocytes

Author: Fabienne Meggetto, Alan Bénard, Nadine Cogne, Aurélie Chanut, Nathalie Faumont, Georges Delsol, Jean Feuillard, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Centre de Physiopathologie Toulouse Purpan, and Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH : Cell Line, MESH : Molecular Sequence Data, DNA Mutational Analysis, MESH: NF-kappa B, Apoptosis, MESH: Base Sequence, medicine.disease_cause, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH: Luciferases, Renilla, immune system diseases, hemic and lymphatic diseases, MESH : Hodgkin Disease, Tumor Cells, Cultured, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Viral Matrix Proteins, MESH: Genetic Variation, Reed-Sternberg Cells, MESH: DNA Mutational Analysis, MESH : Immunoblotting, MESH: Reed-Sternberg Cells, Oncogene Proteins, Genetics, B-Lymphocytes, 0303 health sciences, Mutation, MESH: Immunoblotting, MESH : Oncogene Proteins, NF-kappa B, Hematology, Transfection, Hodgkin Disease, MESH: Hodgkin Disease, MESH : NF-kappa B, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Mutation, MESH : Transfection, MESH: Mutation, MESH : Recombinant Fusion Proteins, Recombinant Fusion Proteins, Immunoblotting, Molecular Sequence Data, MESH : Luciferases, Renilla, MESH : DNA Mutational Analysis, Biology, MESH: Sequence Homology, Nucleic Acid, MESH : B-Lymphocytes, Cell Line, Viral Matrix Proteins, 03 medical and health sciences, MESH: Oncogene Proteins, stomatognathic system, MESH : Genetic Variation, Sequence Homology, Nucleic Acid, MESH: B-Lymphocytes, medicine, otorhinolaryngologic diseases, MESH: Recombinant Fusion Proteins, Animals, Humans, Hodgkin's Lymphoma, MESH : Sequence Homology, Nucleic Acid, MESH: Tumor Cells, Cultured, Luciferases, Renilla, 030304 developmental biology, MESH: Viral Matrix Proteins, MESH: Molecular Sequence Data, MESH: Humans, MESH : Reed-Sternberg Cells, Base Sequence, MESH: Apoptosis, MESH: Transfection, MESH : Humans, Genetic Variation, medicine.disease, Hodgkin's lymphoma, Epstein–Barr virus, Lymphoma, MESH: Cell Line, stomatognathic diseases, Reed–Sternberg cell, Cell culture, Cancer research, MESH : Base Sequence, MESH : Animals, Carcinogenesis, MESH : Apoptosis
Abstract: International audience; BACKGROUND: In Epstein-Barr virus-associated Hodgkin's lymphomas, neoplastic Reed-Sternberg cells and surrounding non-tumor B-cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-cells. DESIGN AND METHODS: Twelve LMP1 natural variants from Reed-Sternberg cells, non-tumor B-cells of Hodgkin's lymphomas and from B-cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 cells to search for relationships between LMP1 cellular origin and oncogenic properties as well as nuclear factor-kappaB activation, and apoptosis protection. RESULTS: LMP1 variants of Reed-Sternberg cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg cells, but inconstantly for LMP1-variants from non-tumor B-cells. Analysis of LMP1 variants from both normal B-cells and Reed-Sternberg cells indicates that protection against apoptosis through activation of nuclear factor-kappaB - whatever the cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. CONCLUSIONS: Taken together, our results demonstrate that preserved nuclear factor-kappaB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor cells in Hodgkin's lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg cells.
Published: 2009
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12. Stepwise development of MAIT cells in mouse and human

Author: Claire Soudais, Ivan C. Moura, Stéphane Cherif, Hélène Laude, Emmanuel Martin, Lucia Guerri, Cécile Toly, Livine Duban, Anne Devys, Florence Tilloy, Sylvain Latour, Virginie Premel, Gabriella Vera, Olivier Lantz, Emmanuel Treiner, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm U925, équipe avenir, Développement normal et pathologique des lymphocytes et signalisation, Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang [Nantes], Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from INSERM, Action incitative (ACI) 'physiologie integrative,' Agence Nationale pour la Recherche (ANR), and Section Médicale de l'Institut Curie. The development of the 3C10 antibody was funded in part by Innate-Pharma (Marseille, France). OL is supported by la Ligue Contre le Cancer as an 'équipe labellisée.', Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Immunité et cancer (U932), and Autard, Delphine
Subjects: Adoptive cell transfer, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH : Kruppel-Like Transcription Factors, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, MESH: Histocompatibility Antigens Class I, Mice, 0302 clinical medicine, MESH : Child, T-Lymphocyte Subsets, MESH: Child, Cytotoxic T cell, Promyelocytic Leukemia Zinc Finger Protein, MESH: Animals, Biology (General), Child, Mice, Knockout, 0303 health sciences, B-Lymphocytes, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, MESH : Immunity, Mucosal, General Neuroscience, Natural killer T cell, Fetal Blood, MESH : Mice, Transgenic, Cell biology, MESH : Receptors, Antigen, T-Cell, alpha-beta, MESH : Histocompatibility Antigens Class I, MESH: Kruppel-Like Transcription Factors, Antibody, General Agricultural and Biological Sciences, Research Article, Genetically modified mouse, MESH: Mice, Transgenic, QH301-705.5, Immunology, Kruppel-Like Transcription Factors, Mice, Transgenic, Mucosal associated invariant T cell, Thymus Gland, Major histocompatibility complex, General Biochemistry, Genetics and Molecular Biology, MESH : B-Lymphocytes, Minor Histocompatibility Antigens, 03 medical and health sciences, MESH: B-Lymphocytes, MESH : Mice, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, MESH : Thymus Gland, MESH: Fetal Blood, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Immunity, Mucosal, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH : T-Lymphocytes, MESH : Fetal Blood, MESH: Humans, General Immunology and Microbiology, T-cell receptor, Histocompatibility Antigens Class I, MESH : Humans, MESH: Thymus Gland, MESH : Natural Killer T-Cells, MESH : T-Lymphocyte Subsets, Gastrointestinal Tract, MESH: T-Lymphocytes, MESH: Natural Killer T-Cells, MESH: Immunity, Mucosal, biology.protein, Natural Killer T-Cells, MESH : Mice, Knockout, MESH: Gastrointestinal Tract, MESH : Animals, MESH : Gastrointestinal Tract, 030215 immunology
Abstract: Mucosal-associated invariant T (MAIT) cells display two evolutionarily conserved features: an invariant T cell receptor (TCR)α (iTCRα) chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC) molecule, MHC-related molecule 1 (MR1). MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanVα7.2 antibody and MAIT cell-specific iTCRα and TCRβ transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRα and TCRβ transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT) cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%–4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the periphery in a process dependent both upon B cells and the bacterial flora. Thus, their development follows a unique pattern at the crossroad of NKT and γδ T cells., Author Summary White blood cells, or lymphocytes, play an important role in defending the body from infection and disease. T lymphocytes come in many varieties with diverse functions. Mucosal-associated invariant T (MAIT) cells constitute a subset of unconventional T lymphocytes, characterized by their invariant T cell receptor (TCR)α chain and their requirement for the nonpolymorphic class Ib (MHC) molecule, MR1. MAIT cells are extremely abundant in human blood and mucosae. Contrary to mainstream T cells, their development requires B cells and commensal microbial flora. To shed light on the little-understood MAIT cells, we used new tools, including an antibody that we recently developed to detect human MAIT cells, and we were able to show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. We show that thymic selection is MR1 dependent but requires neither B cells nor the commensal flora, which are both necessary for the expansion in the periphery. In contrast with the other evolutionarily conserved invariant subset, the natural killer T (NKT) cells, we found that MAIT cells exit the thymus as “naïve” cells before becoming antigen-experienced memory cells and expanding in number to represent a significant 1%–4% of peripheral T cells in human blood. In mice, we found that MAIT cells remain naïve and do not expand substantially. We conclude that MAIT cell development follows a unique scheme, where, unlike NKT cells, MAIT cell selection and expansion are uncoupled events that are mediated by distinct cell types in different compartments., Mucosal-associated invariant T cells, the most abundant invariant T cell subset in humans, arise via a distinct developmental pathway that represents a hybrid of that seen for NKT and γδ T cells, two other unconventional T cell subsets.
Published: 2009
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13. Role of regulatory T cells in a new mouse model of experimental autoimmune myositis

Author: Yves Allenbach, Benoît L. Salomon, Odile Dubourg, S. Solly, Serge Herson, Lucile Musset, Olivier Benveniste, Sylvie Grégoire, David Klatzmann, Gillian Butler-Browne, Facultat de Química (DEPARTAMENT DE QUíMICA ORGàNICA), Universitat de Barcelona (UB), Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires (CNRS UMR 7087), Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, UMR S 787, Université Pierre et Marie Curie - Paris 6 (UPMC), EA 209 - Transports membranaires et chimiorésistances (LABORATOIRE DE PARASITOLOGIE-MYCOLOGIE), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5), Service de biothérapies [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Facultat de Química ( DEPARTAMENT DE QUíMICA ORGàNICA ), Universitat de Barcelona ( UB ), Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires ( CNRS UMR 7087 ), Centre National de la Recherche Scientifique ( CNRS ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Université Pierre et Marie Curie - Paris 6 ( UPMC ), EA 209 - Transports membranaires et chimiorésistances ( LABORATOIRE DE PARASITOLOGIE-MYCOLOGIE ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de cardiologie et maladies vasculaires [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biologie et thérapeutique des pathologies immunitaires (BTPI), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Inflammation, CD4-Positive T-Lymphocytes, MESH : Immunohistochemistry, MESH: Interleukin-2 Receptor alpha Subunit, medicine.disease_cause, Polymyositis, T-Lymphocytes, Regulatory, Autoimmunity, Nervous System Autoimmune Disease, Experimental, MESH : T-Lymphocytes, Regulatory, Mice, 0302 clinical medicine, MESH: Autoimmune Diseases, MESH : Female, MESH: Animals, IL-2 receptor, MESH : Muscle, Skeletal, Myositis, 0303 health sciences, education.field_of_study, MESH: Muscle, Skeletal, B-Lymphocytes, Mice, Inbred BALB C, MESH: Muscle Strength, MESH: CD4-Positive T-Lymphocytes, MESH : Interleukin-2 Receptor alpha Subunit, Immunohistochemistry, 3. Good health, MESH : CD4-Positive T-Lymphocytes, MESH: Immunization, Female, medicine.symptom, MESH : Nervous System Autoimmune Disease, Experimental, Population, MESH: Mice, Inbred BALB C, Inflammation, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, MESH : Myosins, Muscle disorder, Biology, Myosins, Pathology and Forensic Medicine, MESH : B-Lymphocytes, Autoimmune Diseases, MESH: Nervous System Autoimmune Disease, Experimental, 03 medical and health sciences, MESH : Autoimmune Diseases, MESH: B-Lymphocytes, MESH : Mice, medicine, Animals, Muscle Strength, education, Muscle, Skeletal, MESH: Mice, MESH : Mice, Inbred BALB C, 030304 developmental biology, MESH : Inflammation, MESH: T-Lymphocytes, Regulatory, Interleukin-2 Receptor alpha Subunit, MESH: Immunohistochemistry, MESH : Immunization, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, MESH: Myosins, medicine.disease, MESH : Muscle Strength, Immunology, Immunization, MESH : Animals, MESH: Female, CD8, 030215 immunology, Regular Articles
Abstract: International audience; Polymyositis is a rare and severe inflammatory muscle disorder. Treatments are partially efficacious but have many side effects. New therapeutic approaches must be first tested in a relevant animal model. Regulatory CD4+CD25+ T cells (Tregs) have been rediscovered as a pivotal cell population in the control of autoimmunity, but the connection between polymyositis and Tregs is currently unknown. To develop a reproducible experimental autoimmune myositis model of polymyositis, mice were immunized once a week for 3 weeks with 1 mg of partially purified myosin emulsified in complete Freund's adjuvant. All mice injected with myosin and complete Freund's adjuvant developed myositis. The infiltrates were composed of CD4(+) and CD8(+) cells, as well as macrophages, but did not contain B lymphocytes. In mice that were depleted of Tregs, the myositis was more severe, as determined by quantitative scoring of muscle inflammation (2.36 +/- 0.9 vs. 1.64 +/- 0.8, P = 0.019). In contrast, injection of in vitro expanded polyclonal Tregs at the time of immunization significantly improved the disease (quantitative score of inflammation 0.87 +/- 1.06 vs. 2.4 +/- 0.67, P = 0.047). Transfer of sensitized or CD4(+)-sorted cells from the lymph nodes of experimental autoimmune myositis mice induced myositis in naïve, irradiated, recipient mice. Thus, experimental autoimmune myositis is a reproducible, transferable disease in mice, both aggravated by Treg depletion and improved by polyclonal Treg injection.
Published: 2009
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14. Tetrameric and homodimeric camelid IgGs originate from the same IgH locus

Author: Pierre Lafaye, Patricia Cavelier, Ikbel Achour, François Rougeon, Christiane Bouchier, Magali Tichit, Génétique et Biochimie du Développement, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Génomique (Plate-Forme), Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris] (IP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: MESH: Immunoglobulins, MESH : Molecular Sequence Data, MESH: Amino Acid Sequence, MESH: Base Sequence, MESH : Immunoglobulins, 0302 clinical medicine, Immunology and Allergy, MESH: Animals, MESH: Phylogeny, Peptide sequence, Phylogeny, Genetics, 0303 health sciences, B-Lymphocytes, biology, MESH : Amino Acid Sequence, MESH: Camels, MESH : Protein Binding, Translocon, medicine.anatomical_structure, MESH : Dimerization, Cosmid, MESH: Camelids, New World, Antibody, Camelids, New World, Dimerization, Protein Binding, Camelus, MESH : Cell Membrane, Immunology, Molecular Sequence Data, Immunoglobulins, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, MESH : B-Lymphocytes, 03 medical and health sciences, Complementary DNA, MESH: B-Lymphocytes, medicine, MESH: Protein Binding, Animals, Amino Acid Sequence, Gene, B cell, 030304 developmental biology, MESH: Molecular Sequence Data, MESH : Camels, Base Sequence, Cell Membrane, MESH : Phylogeny, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Molecular biology, MESH : Camelids, New World, Chromosome 4, MESH: Dimerization, biology.protein, MESH : Base Sequence, MESH : Animals, 030215 immunology, MESH: Cell Membrane
Abstract: In addition to producing conventional tetrameric IgGs, camelids have the particularity of producing a functional homodimeric IgG type lacking L (light) chains and only made up of two H (heavy) chains. This nonconventional IgG type is characterized by variable and constant regions referred to as VHH and CHH, respectively, and which differ from conventional VH and CH counterparts. Although the structural properties of homodimeric IgGs have been well investigated, the genetic bases involved in their generation are still largely unknown. In this study, we characterized the organization of genes coding for the H chains of tetrameric and homodimeric IgGs by constructing an alpaca (Lama pacos) genomic cosmid library. We showed that a single IgH locus in alpaca chromosome 4 contains all of the genetic elements required for the generation of the two types of Igs. The alpaca IgH locus is composed of a V region that contains both VHH and VH genes followed by a unique DH-JH cluster and C region genes, which include both CHH and CH genes. Although this general gene organization greatly resembles that of other typical mammalian Vn-Dn-Jn-Cn translocon IgH loci, the intermixed gene organization within the alpaca V and C regions reveals a new type of translocon IgH locus. Furthermore, analyses of cDNA coding for the membrane forms of IgG and IgM present in alpaca peripheral blood B cells are most consistent with the notion that the development of a B cell bearing homodimeric IgG passes through an IgM+ stage, similar to the case for conventional IgG.
Published: 2008
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15. Cell surface expression of the bovine leukemia virus-binding receptor on B and T lymphocytes is induced by receptor engagement

Author: Amélie Montel-Hagen, Cédric Mongellaz, Marc Sitbon, Jean-Luc Battini, Sandrina Kinet, Naomi Taylor, Madakasira Lavanya, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Génétique Moléculaire de Montpellier ( IGMM ), and Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH : Leukemia Virus, Bovine, Receptor expression, T-Lymphocytes, animal diseases, viruses, T-cell leukemia, MESH: Rabbits, Lymphocyte Activation, MESH: Deltaretrovirus, Mice, MESH: Leukemia Virus, Bovine, MESH: Protein Structure, Tertiary, 0302 clinical medicine, MESH : Deltaretrovirus, Viral Envelope Proteins, immune system diseases, MESH : Cattle, Leukemia Virus, Bovine, MESH: Up-Regulation, Immunology and Allergy, MESH: Animals, Receptor, MESH : Up-Regulation, MESH: Antigens, CD, Cells, Cultured, 0303 health sciences, B-Lymphocytes, Bovine leukemia virus, virus diseases, 3. Good health, Up-Regulation, Interleukin 10, MESH: Cattle, MESH : Viral Envelope Proteins, Interleukin-21 receptor, Receptors, Virus, Rabbits, MESH : Protein Structure, Tertiary, MESH: Cells, Cultured, MESH : Interleukin-7, MESH: Cell Line, Tumor, MESH : Recombinant Fusion Proteins, Recombinant Fusion Proteins, Immunology, B-cell receptor, Thymus Gland, Biology, Deltaretrovirus, MESH : B-Lymphocytes, 03 medical and health sciences, Antigens, CD, Cell Line, Tumor, MESH: B-Lymphocytes, MESH : Mice, MESH : Cells, Cultured, MESH : Antigens, CD, MESH: Recombinant Fusion Proteins, Animals, Humans, MESH : Rabbits, MESH : Thymus Gland, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Lymphocyte Activation, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, MESH : Lymphocyte Activation, 030304 developmental biology, Common gamma chain, MESH : T-Lymphocytes, MESH: Humans, MESH : Cell Line, Tumor, Interleukin-7, MESH : Humans, MESH: Thymus Gland, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Virology, MESH: Receptors, Virus, MESH: Interleukin-7, Protein Structure, Tertiary, MESH: T-Lymphocytes, MESH: Viral Envelope Proteins, Cattle, MESH : Animals, MESH : Receptors, Virus, 030215 immunology
Abstract: Bovine leukemia virus (BLV), one of the most common infectious viruses of cattle, is endemic in many herds. Approximately 30–40% of adult cows in the United States are infected by this oncogenic C-type retrovirus and 1–5% of animals will eventually develop a malignant lymphoma. BLV, like the human and simian T cell leukemia viruses, is a deltaretrovirus but, in contrast with the latter, the BLV receptor remains unidentified. In this study, we demonstrate that the amino-terminal 182 residues of the BLV envelope glycoprotein surface unit encompasses the receptor-binding domain. A bona fide interaction of this receptor-binding domain with the BLV receptor was demonstrated by specific interference with BLV, but not human T cell leukemia virus, envelope glycoprotein-mediated binding. We generated a rabbit Ig Fc-tagged BLV receptor-binding domain construct and ascertained that the ligand binds the BLV receptor on target cells from multiple species. Using this tool, we determined that the BLV-binding receptor is expressed on differentiating pro/pre-B cells in mouse bone marrow. However, the receptor was not detected on mature/quiescent B cells but was induced upon B cell activation. Activation of human B and T lymphocytes also induced surface BLV-binding receptor expression and required de novo protein synthesis. Receptor levels were down-regulated as activated lymphocytes returned to quiescence. In the human thymus, BLV-binding receptor expression was specifically detected on thymocytes responding to the IL-7 cytokine. Thus, expression of the BLV-binding receptor is a marker of enhanced metabolic activity in B cells, T cells, and thymocytes.
Published: 2008
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16. Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cells

Author: Pierre Charneau, Julia Hauer, Julie Rivière, Marc Le Lorc'h, Jean-Pierre de Villartay, Pauline Soulas-Sprauel, Anne Galy, Michèle Malassis-Séris, Johanna Blondeau, Alexandrine Garrigue, Alain Fischer, Frederique Pâques, Nicole Brousse, Marina Cavazzana-Calvo, Serge Romana, Fatine Benjelloun, Daniel Stockholm, Annick Lim, Corinne Demerens-de Chappedelaine, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Généthon, Développement des Lymphocytes, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Histologie-Embryologie et Cytogénétique Assistance Publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et Cytologie Pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Cellectis SA, CELLECTIS, Virologie moléculaire et Vectorologie, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Unité d'Immunologie et Hématologie Pédiatrique, Service d'Hématologie, Département de Biothérapie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), This work was funded by grants from Institut National de la Santé et de la Recherche (INSERM), the Association Française contre les Myopathies (AFM) contract GAT0203, the Consortium National de Recherche en Génomique, the EC contract QLK3-CT-1999-00859, the Consert contract no. 005242, the Inherinet contract QLK3-CT-2001-00427, the Agence Nationale de la Recherche grant 05-MRAR-004, and a grant from Amgen-France (M. de Garidel and C. Cailliot). F.B.'s fellowship was provided by the AFM. P.S.S. was supported by INSERM, Electricité de France, and the Fondation Singer Polignac. J.H. is a fellow of the Deutsche Akademie der Naturforscher Leopoldina (BMBF-LPD 9901/8-149), Immunologie moléculaire et biothérapies innovantes (IMBI), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Genethon, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], and CHU Necker - Enfants Malades [AP-HP]-Université Paris Descartes - Paris 5 (UPD5)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, CD3 Complex, MESH: Antigens, CD3, Genetic enhancement, T-Lymphocytes, MESH: Interleukin-2 Receptor alpha Subunit, MESH: Antigens, CD4, MESH: Flow Cytometry, MESH: Mice, Knockout, MESH: Hematopoietic Stem Cells, Mice, 0302 clinical medicine, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Genetic Vectors, Transduction, Genetic, Chromosome instability, MESH : Antigens, CD44, Drug Discovery, MESH : Female, MESH: Animals, Cells, Cultured, MESH: Lentivirus, Mice, Knockout, 0303 health sciences, B-Lymphocytes, Hematopoietic Stem Cell Transplantation, Nuclear Proteins, MESH : Interleukin-2 Receptor alpha Subunit, MESH: Transduction, Genetic, Flow Cytometry, MESH : Genetic Vectors, 3. Good health, Haematopoiesis, MESH : Lentivirus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Hyaluronan Receptors, 030220 oncology & carcinogenesis, Knockout mouse, CD4 Antigens, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Medicine, Female, Stem cell, MESH : Gene Therapy, MESH: Cells, Cultured, MESH : Flow Cytometry, MESH : Male, CD8 Antigens, Genetic Vectors, MESH : Severe Combined Immunodeficiency, MESH: Severe Combined Immunodeficiency, MESH : Transduction, Genetic, Thymus Gland, Biology, MESH: Antigens, CD44, MESH : B-Lymphocytes, Viral vector, 03 medical and health sciences, MESH : Hematopoietic Stem Cell Transplantation, MESH: B-Lymphocytes, MESH : Mice, MESH : Cells, Cultured, Genetics, medicine, Animals, MESH : Thymus Gland, Molecular Biology, MESH: Mice, MESH: Hematopoietic Stem Cell Transplantation, 030304 developmental biology, MESH : T-Lymphocytes, Pharmacology, Severe combined immunodeficiency, MESH : Hematopoietic Stem Cells, Lentivirus, Interleukin-2 Receptor alpha Subunit, MESH : Nuclear Proteins, MESH: Thymus Gland, Genetic Therapy, medicine.disease, Endonucleases, Hematopoietic Stem Cells, MESH: Male, Transplantation, MESH: T-Lymphocytes, Immunology, Cancer research, MESH : Mice, Knockout, MESH : Antigens, CD4, Severe Combined Immunodeficiency, MESH : Animals, MESH : Antigens, CD3, MESH: Antigens, CD8, MESH: Gene Therapy, MESH : Antigens, CD8, MESH: Nuclear Proteins, MESH: Female
Abstract: International audience; Patients with mutations in the Artemis gene display a complete absence of T- and B lymphocytes, together with increased cellular radiosensitivity; this leads to a radiosensitive severe combined immunodeficiency (RS-SCID). Allogenic hematopoietic stem-cell (HSC) transplantation is only partially successful in the absence of an human leukocyte antigen-genoidentical donor, and this has prompted a search for alternative therapeutic approaches such as gene therapy. In this study, a self-inactivated lentiviral vector expressing Artemis was used to complement the Artemis knockout mouse (Art(-/-)). Transplantation of Artemis-transduced HSCs into irradiated Art(-/-) mice restored a stable (over a 15-month period of follow-up) and functional T- and cell repertoire that was comparable to that of control mice. The success of secondary transplantations demonstrated that the HSCs had been transduced. One of thirteen mice developed a thymoma 6 months after gene therapy. Although thymic cells were seen to be carrying two lentiviral integration sites, there was no evidence of lentivirus-driven oncogene activation. The Art(-/-) mice were found to be prone to develop T-cell lymphomas, either spontaneously or after irradiation. These data indicate that the observed lymphoproliferation was probably the consequence of the chromosomal instability associated with the Artemis-deficient background. As a whole, our work provides a basis for supporting the gene therapy approach in Artemis-deficient SCID.
Published: 2008
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17. Lentiviral transduction of immune cells

Author: Swainson, Louise, Mongellaz, Cedric, Adjali, Oumeya, Vicente, Rita, Taylor, Naomi, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: T-Lymphocytes, Centrifugation, MESH : Promoter Regions, Genetic, MESH: Titrimetry, MESH: Hematopoietic Stem Cells, Mice, MESH: Genetic Vectors, Transduction, Genetic, MESH: Animals, Transgenes, Promoter Regions, Genetic, Cells, Cultured, MESH: Lentivirus, B-Lymphocytes, MESH: Dendritic Cells, MESH: Centrifugation, Titrimetry, MESH: Transduction, Genetic, MESH : Genetic Vectors, MESH: Leukocytes, Mononuclear, MESH : Lentivirus, MESH: Virion, MESH : Transfection, MESH : Transgenes, MESH: Cells, Cultured, Plasmids, Genetic Vectors, MESH: Transgenes, MESH : Transduction, Genetic, Transfection, MESH : B-Lymphocytes, MESH: Plasmids, MESH: B-Lymphocytes, MESH : Titrimetry, MESH: Promoter Regions, Genetic, MESH : Cells, Cultured, MESH : Mice, MESH : Virion, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : T-Lymphocytes, MESH: Transfection, MESH : Hematopoietic Stem Cells, Lentivirus, Virion, Dendritic Cells, Hematopoietic Stem Cells, MESH : Leukocytes, Mononuclear, MESH: T-Lymphocytes, MESH : Plasmids, MESH : Dendritic Cells, MESH : Centrifugation, Leukocytes, Mononuclear, MESH : Animals
Abstract: International audience; Gene transfer into mammalian cells has been of crucial importance for studies determining the role of specific genes in the differentiation and cell fate of various hematopoietic lineages. Until recently, the majority of these studies were performed in transformed cell lines due to difficulties in achieving levels of transfection of greater than 1-3% in primary hematopoietic cells. Vectors based on retrovirus and lentivirus backbones have revolutionized our ability to transfer genes into primary hematopoietic cells. These vectors have allowed extensive ex vivo and in vivo studies following introduction of a gene of interest and have been used clinically in individuals suffering from cancers, infections, and genetic diseases. Ex vivo lentiviral gene transfer can result in efficient transduction of progenitor cells (>80%) that can then be further differentiated into immune lineage cells including T, B, dendritic, or natural killer cells. Alternatively, differentiated immune cells can themselves be transduced ex vivo with lentiviral vectors. Here, we discuss optimization of technologies for human immunodeficiency virus (HIV)-based gene transfer into murine and human progenitor and immune cell lineages.
Published: 2008
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18. Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patients

Author: Alain Fischer, Pierre Charneau, Chantal Lagresle-Peyrou, Monique Forveille, Kheira Beldjord, Christophe Hue, Fatine Benjelloun, Marina Cavazzana-Calvo, Isabelle André-Schmutz, Salima Hacein-Bey-Abina, Delphine Bonhomme, Jean-Pierre de Villartay, Anne Durandy, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cythéris, Laboratoire d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biothérapie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service d'Hématologie, Virologie moléculaire et Vectorologie, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service d'Immunologie et d'Hématologie Pédiatriques, This work was supported by grants from INSERM, Association Française contre les Myopathies (AFM) contract GAT0203, Consortium National de Recherche en Génomique, EC contract QLK3-CT-1999-00859, Consert no. 005242, Inherinet contract QLK3-CT-2001-00427, Agene nationale de la recherche 05-MRAR-004 and Amgen-France, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP]-Université Paris Descartes - Paris 5 (UPD5)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Mice, Inbred NOD, Genetic enhancement, CD34, Antigens, CD34, Mice, SCID, MESH: Antibodies, Monoclonal, Mice, 0302 clinical medicine, Mice, Inbred NOD, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Drug Discovery, MESH: Animals, MESH : Homeodomain Proteins, MESH: Mice, SCID, MESH: Bone Marrow Transplantation, Bone Marrow Transplantation, MESH: Lentivirus, B-Lymphocytes, 0303 health sciences, biology, MESH: Bone Marrow Cells, Antibodies, Monoclonal, Nuclear Proteins, Cell Differentiation, MESH: Immunoglobulin M, 3. Good health, DNA-Binding Proteins, MESH: Interleukin-2 Receptor beta Subunit, MESH : Lentivirus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH : Antibodies, Monoclonal, 030220 oncology & carcinogenesis, MESH : Antigens, CD34, Molecular Medicine, Antibody, MESH : Cell Differentiation, MESH: Cell Differentiation, MESH : Immunoglobulin M, Bone Marrow Cells, Human leukocyte antigen, Recombination-activating gene, MESH : B-Lymphocytes, 03 medical and health sciences, Antigen, MESH: B-Lymphocytes, MESH : Mice, MESH: Homeodomain Proteins, Genetics, medicine, Animals, Humans, Molecular Biology, MESH: Mice, MESH : Interleukin-2 Receptor beta Subunit, 030304 developmental biology, Homeodomain Proteins, Pharmacology, Severe combined immunodeficiency, MESH: Humans, MESH : Mice, Inbred NOD, Lentivirus, MESH : Humans, MESH : Nuclear Proteins, MESH : Bone Marrow Transplantation, MESH: Antigens, CD34, Endonucleases, medicine.disease, MESH : Mice, SCID, Interleukin-2 Receptor beta Subunit, Transplantation, Immunoglobulin M, Immunology, biology.protein, Cancer research, MESH : Animals, MESH: Nuclear Proteins, MESH : Bone Marrow Cells
Abstract: International audience; Severe combined immunodeficiency (SCID) caused by mutation of the recombination-activating gene 1 (RAG1) or Artemis gene lead to the absence of B- and T-cell differentiation. The only curative treatment is allogeneic bone marrow (BM) transplantation, which displays a high survival rate when an HLA compatible donor is available but has a poorer prognosis when the donor is partially compatible. Consequently, gene therapy may be a promising alternative strategy for these diseases. Here, we report that lentiviral gene-corrected BM CD34(+) cells (isolated from Artemis- or RAG1-deficient patients) sustain human B-cell differentiation following injection into non-obese diabetic/SCID (NOD-SCID) mice previously infused with anti-interleukin-2 receptor beta chain monoclonal antibody. In most of the mice BM, engrafted with Artemis-transduced cells, human B-cell differentiation occurred until the mature stage. The B cells were functional as human immunoglobulin M (IgM) was present in the serum. Following injection with RAG1-transduced cells, human engraftment occurred in vivo but B-cell differentiation until the mature stage was less frequent. However, when it occurred, it was always associated with human IgM production. This overall approach represents a useful tool for evaluating gene transfer efficiency in human SCID forms affecting B-cell development (such as Artemis deficiency) and for testing new vectors for improving in vivo RAG1 complementation.
Published: 2008
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19. Pathophysiological aspects of memory B-cell development

Author: Olivier Hermine, Sandrine Roulland, Bertrand Nadel, Felipe Suarez, Slama, Catherine, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Immunoglobulins, Cellular differentiation, T-Lymphocytes, Follicular lymphoma, Hepacivirus, MESH : Hepacivirus, MESH : Immunoglobulins, MESH: Lymphoma, Follicular, 0302 clinical medicine, MESH: Germinal Center, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Hepacivirus, Memory B cell, MESH: Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH: Plasma Cells, B-Lymphocytes, Cell Differentiation, Marginal zone, Antigens, T-Independent, MESH : Antigens, T-Independent, MESH : Lymphoma, B-Cell, Marginal Zone, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Immunologic Memory, MESH : Helicobacter pylori, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Cell Differentiation, MESH: Cell Differentiation, MESH : Plasma Cells, MESH : Immunologic Memory, Immunology, Plasma Cells, Immunoglobulins, Biology, MESH : B-Lymphocytes, 03 medical and health sciences, Antigen, MESH: B-Lymphocytes, medicine, Animals, Humans, B cell, 030304 developmental biology, MESH : T-Lymphocytes, MESH: Humans, Helicobacter pylori, MESH : Lymphoma, Follicular, MESH : Humans, Germinal center, Lymphoma, B-Cell, Marginal Zone, medicine.disease, Germinal Center, Lymphoma, MESH: T-Lymphocytes, MESH: Antigens, T-Independent, MESH: Helicobacter pylori, MESH : Animals, MESH : Germinal Center, Immunologic Memory
Abstract: B cells follow two functionally distinct pathways of development: a classical germinal center (GC) T-dependent pathway in which diversification and maturation generate a slow, but virtually unlimited high-affinity response to cognate antigens; and a marginal zone (MZ) T-independent pathway providing a first line of 'innate-like' defense against specific pathogens. Cells populating these two distinct locations are the normal counterparts of two clinically important pathological entities, follicular lymphoma (FL) and MZ lymphoma (MZL). FL and MZ represent paradigms of two rising concepts of lymphomagenesis, protracted preclinical and antigen-driven lymphoproliferation, respectively. Integrating the mechanisms and functions of MZ and GC B cells and the distinctive features of their pathological counterparts should provide essential clues to the understanding of their malignant development, and should offer new insights into the design of effective treatments for B-cell lymphomas.
Published: 2008
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20. Role for DNA repair factor XRCC4 in immunoglobulin class switch recombination

Author: Pierre Charneau, Christelle Olivier-Martin, Jean-Pierre de Villartay, Gwenaël Le Guyader, Paola Rivera-Munoz, Vincent Abramowski, Pauline Soulas-Sprauel, Cécile Goujet-Zalc, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Transgenèse et archivage d'animaux modèles (TAAM), Centre National de la Recherche Scientifique (CNRS), Virologie moléculaire et Vectorologie, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Transgenèse et archivage d'animaux modèles ( TAAM ), Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: DNA Repair, medicine.disease_cause, MESH: Mice, Knockout, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH : DNA Repair, Immunology and Allergy, MESH: Animals, MESH: Lentivirus, Mice, Knockout, MESH: DNA Repair, B-Lymphocytes, 0303 health sciences, Mutation, Articles, DNA repair protein XRCC4, MESH : Mice, Transgenic, DNA-Binding Proteins, Non-homologous end joining, MESH : Lentivirus, 030220 oncology & carcinogenesis, MESH: Immunoglobulin Class Switching, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : DNA-Binding Proteins, MESH : Mutation, MESH: Mutation, DNA repair, MESH: Mice, Transgenic, Immunology, Mice, Transgenic, chemical and pharmacologic phenomena, Biology, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Article, Immunoglobulin Class Switch Recombination, MESH : B-Lymphocytes, 03 medical and health sciences, MESH: B-Lymphocytes, MESH : Mice, medicine, Animals, MESH : Immunoglobulin Class Switching, MESH: Mice, 030304 developmental biology, Lentivirus, DNA Repair Pathway, Immunoglobulin Class Switching, Molecular biology, chemistry, Immunoglobulin class switching, MESH : Genes, Lethal, MESH : Mice, Knockout, Genes, Lethal, MESH : Animals, MESH: Genes, Lethal, DNA, MESH: DNA-Binding Proteins
Abstract: International audience; V(D)J recombination and immunoglobulin class switch recombination (CSR) are two somatic rearrangement mechanisms that proceed through the introduction of double-strand breaks (DSBs) in DNA. Although the DNA repair factor XRCC4 is essential for the resolution of DNA DSB during V(D)J recombination, its role in CSR has not been established. To bypass the embryonic lethality of XRCC4 deletion in mice, we developed a conditional XRCC4 knockout (KO) using LoxP-flanked XRCC4 cDNA lentiviral transgenesis. B lymphocyte restricted deletion of XRCC4 in these mice lead to an average two-fold reduction in CSR in vivo and in vitro. Our results connect XRCC4 and the nonhomologous end joining DNA repair pathway to CSR while reflecting the possible use of an alternative pathway in the repair of CSR DSB in the absence of XRCC4. In addition, this new conditional KO approach should be useful in studying other lethal mutations in mice.
Published: 2007
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21. The SH2 domain-containing inositol 5-phosphatase SHIP1 is recruited to the intracytoplasmic domain of human FcgammaRIIB and is mandatory for negative regulation of B cell activation

Author: Marc Daëron, Wolf H. Fridman, Georges Bismuth, Pierre Bruhns, Isabelle Isnardi, Allergologie Moléculaire et Cellulaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie Cellulaire et Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopharmacologie Moléculaire, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Detchepare, Christine, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR58-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UMR_S567 / UMR 8104 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Signal Transduction, Cytoplasm, MESH : Phosphoric Monoester Hydrolases, MESH: Amino Acid Sequence, Lymphocyte Activation, SH2 domain, Mice, chemistry.chemical_compound, MESH: Protein Structure, Tertiary, 0302 clinical medicine, Immunology and Allergy, Inositol, MESH: Animals, Tyrosine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Cells, Cultured, MESH : Receptors, IgG, Sequence Deletion, B-Lymphocytes, 0303 health sciences, MESH : Amino Acid Sequence, breakpoint cluster region, MESH: Sequence Deletion, medicine.anatomical_structure, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases, MESH: Phosphoric Monoester Hydrolases, GRB2, Signal transduction, MESH : Protein Structure, Tertiary, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Signal Transduction, MESH: Cells, Cultured, MESH : Cytoplasm, MESH : Recombinant Fusion Proteins, Recombinant Fusion Proteins, Immunology, Phosphatase, Biology, MESH: Receptors, IgG, MESH : B-Lymphocytes, [ SDV.IMM.ALL ] Life Sciences [q-bio]/Immunology/Allergology, 03 medical and health sciences, MESH: B-Lymphocytes, MESH : Cells, Cultured, MESH : Mice, medicine, MESH: Recombinant Fusion Proteins, Animals, Humans, Amino Acid Sequence, MESH: Lymphocyte Activation, MESH: Mice, MESH : Lymphocyte Activation, B cell, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, MESH : Sequence Deletion, MESH: Cytoplasm, Receptors, IgG, MESH : Humans, Phosphoric Monoester Hydrolases, Protein Structure, Tertiary, chemistry, Cancer research, biology.protein, MESH : Animals, 030215 immunology
Abstract: Murine FcgammaRIIB were demonstrated to recruit SH2 domain-containing inositol 5-phosphatases (SHIP1/2), when their ITIM is tyrosyl-phosphorylated upon co-aggregation with BCR, and SHIP1 to account for FcgammaRIIB-dependent negative regulation of murine B cell activation. Although human FcgammaRIIB share the same ITIM as murine FcgammaRIIB and similarly inhibit human B cell activation, which among the four known SH2 domain-containing (tyrosine or inositol) phosphatases is/are recruited by human FcgammaRIIB is unclear. Our recent finding that, besides the ITIM, a second tyrosine-based motif is mandatory for murine FcgammaRIIB to recruit SHIP1 challenged the possibility that human FcgammaRIIB recruit this phosphatase. Human FcgammaRIIB indeed lack this motif. Using an experimental model which enabled us to compare human FcgammaRIIB and murine FcgammaRIIB under strictly controlled conditions, we show that SHIP1 is recruited to the intracytoplasmic domain of human FcgammaRIIB and inhibits the same biological responses and intracellular signals as when recruited by murine FcgammaRIIB. Identical results were observed in murine and in human B cells. We demonstrate that SHIP is necessary for human FcgammaRIIB to inhibit BCR signaling, and cannot be replaced by SHP-1 or SHP-2. Although it contains no tyrosine, the C-terminal segment of human FcgammaRIIB was as mandatory as the tyrosine-containing C-terminal segment of murine FcgammaRIIB for SHIP1 to be recruited to the ITIM. This segment, however, did not recruit the adapters Grb2/Grap which were demonstrated to stabilize the recruitment of SHIP1 to the ITIM in murine FcgammaRIIB.
Published: 2006
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22. Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study

Author: Lucienne Chatenoud, Loïc Bergougnoux, Augustin Ferrant, Franck Morschhauser, Gérard Socié, Raoul Herbrecht, Peter Vandenberghe, Samira Fafi-Kremer, Noel Milpied, Gilles Salles, Arnaud Jaccard, Véronique Leblond, Alain Fischer, Philippe Lang, Anne Moreau, Walter Feremans, Sylvain Choquet, Patrice Morand, Olivier Hermine, Eric Oksenhendler, Thierry Lamy, Fritz Offner, Etienne Vilmer, Anne-Marie Stoppa, Yvon Lebranchu, Nathalie Berriot-Varoqueaux, Marie-Noëlle Peraldi, Jeanne Luce Garnier, Unité d'hématologie et de transplantation, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Immunologie et d'Hématologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP), Biophysique, Médecine Nucléaire et Technologies Médicales ( EA 1049 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Département de pathologie, Hospices Civils de Lyon ( HCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon, Registre National des Hémopathies malignes de l'Enfant ( RNHE ), Institut de Veille Sanitaire (INVS)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service de néphrologie et immunologie clinique, Hôpital Bretonneau-Université de Tours-CHRU Tours, Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Interaction virus-hôte et maladies du foie, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Virologie moléculaire et structurale, CHU Grenoble, Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biophysique, Médecine Nucléaire et Technologies Médicales (EA 1049), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Registre National des Hémopathies malignes de l'Enfant (RNHE), Institut de Veille Sanitaire (INVS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Bretonneau-Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de virologie moléculaire et structurale (LVMS), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), and Université de Tours (UT)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau
Subjects: Male, MESH: Remission Induction, medicine.medical_treatment, MESH : Prospective Studies, MESH : Aged, Phases of clinical research, Biochemistry, Gastroenterology, Organ transplantation, MESH: Antibodies, Monoclonal, MESH : Organ Transplantation, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, MESH: Lymphoproliferative Disorders, hemic and lymphatic diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Prospective Studies, Prospective cohort study, MESH: Aged, B-Lymphocytes, MESH: Middle Aged, MESH : Lymphoproliferative Disorders, MESH: Hydro-Lyases, Remission Induction, Antibodies, Monoclonal, Immunosuppression, Hematology, MESH : Adult, Middle Aged, 3. Good health, MESH : Antineoplastic Agents, surgical procedures, operative, 030220 oncology & carcinogenesis, MESH : Antibodies, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Disease-Free Survival, Rituximab, Female, medicine.drug, Adult, medicine.medical_specialty, Adolescent, MESH : Male, Immunology, Lymphoproliferative disorders, MESH: Organ Transplantation, MESH : Hydro-Lyases, Antineoplastic Agents, Disease-Free Survival, MESH : B-Lymphocytes, 03 medical and health sciences, Internal medicine, MESH: B-Lymphocytes, MESH : Adolescent, medicine, Humans, MESH : Middle Aged, Hydro-Lyases, Aged, MESH: Adolescent, MESH : Remission Induction, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, Cell Biology, Organ Transplantation, medicine.disease, MESH: Male, MESH: Prospective Studies, Lymphoproliferative Disorders, Surgery, Transplantation, Clinical trial, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, business, MESH: Female, 030215 immunology
Abstract: International audience; B-cell posttransplantation lymphoproliferative disorder (B-PTLD) is a rare but severe complication of transplantation, with no consensus on best treatment practice. This prospective trial, the first to test a treatment for PTLD, was designed to evaluate the efficacy and safety of rituximab in patients with B-PTLD after solid organ transplantation (SOT). Forty-six patients were included and 43 patients were analyzed. Patients were eligible if they had untreated B-PTLD that was not responding to tapering of immunosuppression. Treatment consisted of 4 weekly injections of rituximab at 375 mg/m2. At day (d) 80, 37 (86%) patients were alive, and the response rate was 44.2%, including 12 complete response/unconfirmed complete response (CR/CRu). The only factor predictive of a response at d80 was a normal lactate dehydrogenase level (P = .007, odds ratio [OR] = 6.9). At d360, responses were maintained in 68% of patients, and 56% of patients were alive. The overall survival rate at 1 year was 67%. We conclude that rituximab is effective and safe in PTLD, with stable responses at 1 year. The response rate and overall survival might be improved by combining rituximab with other treatments.
Published: 2005
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23. Dynamics of thymus-colonizing cells during human development

Author: Frederic Jourquin, Rima Haddad, Isabelle André-Schmutz, Cecile Schiffer, Micael Yagello, Niclas Setterblad, Emmanuelle Six, Anne-Lise Delezoide, Bruno Canque, Marina Cavazzana-Calvo, Fabien Guimiot, Françoise Pflumio, Jean Claude Gluckman, Edmond Kahn, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Service de Biologie du Développement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Commun d'Imagerie Cellulaire et Moléculaire, Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Saidi, Vanessa, Laboratoire d'Immunologie Cellulaire et Immunopathologie de l'Ecole Pratique des Hautes Etudes, Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Laboratoire d'Imagerie Fonctionnelle ( LIF ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UMR_S567 / UMR 8104 ), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), and Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: MESH : Bone Marrow, Antigens, Differentiation, T-Lymphocyte, Pathology, MESH: Hematopoietic Stem Cells, Mice, 0302 clinical medicine, Bone Marrow, Cell Movement, Immunology and Allergy, MESH : Cell Movement, MESH: Animals, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, MESH: Antigens, CD, MESH: Cell Movement, MESH : Organ Culture Techniques, 0303 health sciences, education.field_of_study, B-Lymphocytes, Cell Differentiation, Phenotype, MESH : Mice, Transgenic, Cell biology, Haematopoiesis, MESH : Phenotype, MESH : Antigens, Differentiation, T-Lymphocyte, medicine.anatomical_structure, Infectious Diseases, MESH: Bone Marrow, [SDV.IB]Life Sciences [q-bio]/Bioengineering, MESH : Cell Differentiation, MESH: Cell Differentiation, medicine.medical_specialty, MESH: Mice, Transgenic, T cell, Population, Immunology, Mice, Transgenic, Thymus Gland, Biology, MESH: Phenotype, MESH : B-Lymphocytes, 03 medical and health sciences, Organ Culture Techniques, Antigens, CD, MESH: B-Lymphocytes, MESH : Mice, medicine, MESH : Antigens, CD, Animals, Humans, MESH : Thymus Gland, Progenitor cell, education, MESH: Mice, 030304 developmental biology, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Fetus, MESH: Humans, MESH : Hematopoietic Stem Cells, MESH : Humans, MESH: Thymus Gland, Hematopoietic Stem Cells, MESH: Organ Culture Techniques, MESH: Antigens, Differentiation, T-Lymphocyte, Bone marrow, MESH : Animals, Ex vivo, 030215 immunology
Abstract: SummaryHere, we identify fetal bone marrow (BM)-derived CD34hiCD45RAhiCD7+ hematopoietic progenitors as thymus-colonizing cells. This population, virtually absent from the fetal liver (FL), emerges in the BM by development weeks 8–9, where it accumulates throughout the second trimester, to finally decline around birth. Based on phenotypic, molecular, and functional criteria, we demonstrate that CD34hiCD45RAhiCD7+ cells represent the direct precursors of the most immature CD34hiCD1a− fetal thymocytes that follow a similar dynamics pattern during fetal and early postnatal development. Histological analysis of fetal thymuses further reveals that early immigrants predominantly localize in the perivascular areas of the cortex, where they form a lymphostromal complex with thymic epithelial cells (TECs) driving their rapid specification toward the T lineage. Finally, using an ex vivo xenogeneic thymus-colonization assay, we show that BM-derived CD34hiCD45RAhiCD7+ progenitors are selectively recruited into the thymus parenchyma in the absence of exogenous cytokines, where they adopt a definitive T cell fate.
Published: 2005
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24. In vitro functional defects of bone marrow-derived CD34+ progenitors from newly diagnosed mature B-cell malignancies with bone marrow tumor involvement

Author: Frédéric Mauny, Thierry Lamy, Patricia Amé-Thomas, Thierry Fest, Frédéric Deschaseaux, Claude-Eric Bulabois, Jean-Yves Cahn, Patrick Hervé, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ), Hematology, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Microenvironnement cellulaire et moléculaire des tumeurs, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Laboratoire Chrono-environnement (UMR 6249) (LCE), and Université de Rennes (UR)
Subjects: Male, MESH : Bone Marrow, Cancer Research, Pathology, Cell, CD34, MESH : Aged, Antigens, CD34, MESH : Bystander Effect, MESH: Hematopoietic Stem Cells, 0302 clinical medicine, MESH: Lymphoproliferative Disorders, Bone Marrow, MESH : Female, MESH: Aged, 0303 health sciences, B-Lymphocytes, MESH: Middle Aged, MESH : Lymphoproliferative Disorders, MESH: Bystander Effect, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Hematology, Middle Aged, MESH : Adult, MESH: Case-Control Studies, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH : Antigens, CD34, MESH: Bone Marrow, Female, Adult, medicine.medical_specialty, MESH : Case-Control Studies, MESH : Male, Biology, MESH: Bone Marrow Neoplasms, MESH : B-Lymphocytes, 03 medical and health sciences, MESH: B-Lymphocytes, Genetics, medicine, Humans, MESH : Middle Aged, Progenitor cell, Molecular Biology, 030304 developmental biology, Aged, MESH: Humans, CD117, MESH : Hematopoietic Stem Cells, MESH : Humans, Chemotaxis, MESH: Adult, Cell Biology, MESH: Antigens, CD34, Bystander Effect, Hematopoietic Stem Cells, In vitro, MESH: Male, Lymphoproliferative Disorders, MESH : Bone Marrow Neoplasms, Case-Control Studies, Cancer research, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Bone marrow, Bone Marrow Neoplasms, MESH: Female, Ex vivo
Abstract: International audience; OBJECTIVE: We hypothesized that the presence of tumor cells in bone marrow (BM) could alter hematopoietic progenitor cell functions. Therefore, we evaluated phenotypic and in vitro functional properties of BM-derived CD34+ progenitors issued from untreated and newly diagnosed patients presenting a mature B-lymphoproliferative disorder (LPD) involving the BM (Inv+). PATIENTS AND METHODS: In vitro proliferation and differentiation capacities of primitive and committed progenitors were evaluated by cobblestone area-forming cell (CAFC) and colony-forming cell (CFC) assays, and ex vivo cell expansion. Migratory capacities of CD34+ cells were explored by chemotaxis assays using a CXCL12alpha gradient. RESULTS: Our results showed that CD34+ cells from Inv+ patients overexpressed CD117 and had a significant decrease of week-3 and -6 CAFC, and CFC frequencies, compared to cells obtained from healthy volunteers and LPD patients without BM involvement (Inv-). In addition, progenitors from Inv+ patients maintained a significantly decreased CFC capacity after ex vivo cell expansion, compared to healthy volunteers. However, the former cells held their migratory capacity in response to CXCL12alpha. CONCLUSION: Functional defects of primitive and committed CD34+ progenitors detected among LPD patients with BM tumor involvement suggest either that tumor cells may induced bystander effects on progenitors or that "unusual" CD34+ cells may exist in the BM that could belong to the proliferating tumor tissue.
Published: 2005
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25. Normal immune system development in mice lacking the Deltex-1 RING finger domain

Author: Pierre Ferrier, Florence Bernex, Claude-Agnès Reynaud, Christophe Verthuy, Sébastien Storck, Frédéric Delbos, Catherine Thirion-Delalande, Nicolas Stadler, Jean-Claude Weill, Génétique Moléculaire et Cellulaire (UGMC), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), This work was supported by grants from the Ministère de la Recherche (ACI Biologie du Développement et Physiologie Intégrative) and the Fondation Princesse Grace. S.S was supported by grants from the Ministère de l'Education Nationale de la Recherche et de la Technologie and Association pour la Recherche contre le Cancer., Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA) - Ecole Nationale Vétérinaire d'Alfort, Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Haon, Marie Laure, and École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)
Subjects: Antigens, Differentiation, T-Lymphocyte, MESH : Molecular Sequence Data, MESH: Sequence Homology, Amino Acid, MESH: Spleen, T-Lymphocytes, [SDV]Life Sciences [q-bio], MESH: Flow Cytometry, MESH: Amino Acid Sequence, medicine.disease_cause, MESH: Mice, Knockout, VOIE DE SIGNALISATION NOTCH, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, Mammalian Genetic Models with Minimal or Complex Phenotypes, MESH: Animals, Mice, Knockout, Regulation of gene expression, B-Lymphocytes, 0303 health sciences, Mutation, biology, MESH : Amino Acid Sequence, Gene Expression Regulation, Developmental, Flow Cytometry, Antigens, T-Independent, MESH : Sequence Homology, Amino Acid, Ubiquitin ligase, DNA-Binding Proteins, RING finger domain, MESH : Antigens, T-Independent, MESH : Antigens, Differentiation, T-Lymphocyte, medicine.anatomical_structure, Deltex-4, [SDV.IMM]Life Sciences [q-bio]/Immunology, NOTCH SIGNALING PATHWAY, MESH : DNA-Binding Proteins, MESH : Mutation, Deltex-1, MESH : Spleen, Notch, MESH: Mutation, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Flow Cytometry, Ubiquitin-Protein Ligases, Molecular Sequence Data, Notch signaling pathway, Deltex, lymphocyte development, Cell fate determination, ubiquitin ligase, MESH : B-Lymphocytes, 03 medical and health sciences, MESH: B-Lymphocytes, MESH : Mice, medicine, Ring finger, Animals, Amino Acid Sequence, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH : T-Lymphocytes, MESH: Molecular Sequence Data, Sequence Homology, Amino Acid, LIGNAGE T, Germinal center, Cell Biology, Molecular biology, MICE, MESH: T-Lymphocytes, MESH: Antigens, Differentiation, T-Lymphocyte, germinal center, T CELL LINEAGE, biology.protein, MESH: Antigens, T-Independent, MESH : Mice, Knockout, marginal zone, MESH : Animals, MESH : Gene Expression Regulation, Developmental, Spleen, MESH: DNA-Binding Proteins, 030215 immunology
Abstract: The Notch signaling pathway controls several cell fate decisions during lymphocyte development, from T-cell lineage commitment to the peripheral differentiation of B and T lymphocytes. Deltex-1 is a RING finger ubiquitin ligase which is conserved from Drosophila to humans and has been proposed to be a regulator of Notch signaling. Its pattern of lymphoid expression as well as gain-of-function experiments suggest that Deltex-1 regulates both B-cell lineage and splenic marginal-zone B-cell commitment. Deltex-1 was also found to be highly expressed in germinal-center B cells. To investigate the physiological function of Deltex-1, we generated a mouse strain lacking the Deltex-1 RING finger domain, which is essential for its ubiquitin ligase activity. Deltex-1(Delta/Delta) mice were viable and fertile. A detailed histological analysis did not reveal any defects in major organs. T- and B-cell development was normal, as were humoral responses against T-dependent and T-independent antigens. These data indicate that the Deltex-1 ubiquitin ligase activity is dispensable for mouse development and immune function. Possible compensatory mechanisms, in particular those from a fourth Deltex gene identified during the course of this study, are also discussed.
Published: 2005
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26. Human blood IgM 'memory' B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire

Author: C.A. Reynaud, Mary Ellen Conley, Louis M. Staudt, Olivier Tournilhac, J.C. Weill, Jean-Laurent Casanova, Damien Bonnet, Andreas Rosenwald, Sandra K. Weller, Corinne Cordier, Bruce K. Tan, Gil Tchernia, Birte Steiniger, Alessandro Plebani, Moritz C. Braun, D S Kumararatne, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Metabolism Branch, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-Center for Cancer Research-National Institutes of Health, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Immunology, St Jude Children's Research Hospital-The University of Tennessee Health Science Center [Memphis] (UTHSC), Università degli Studi di Brescia [Brescia], Departments of Clinical Immunology and Medicine, Addenbrooke's Hospital, Service de cardiologie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération des maladies infectieuses, CHU Clermont-Ferrand, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institute of Anatomy and Cell Biology, University of Marburg, Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), National Cancer Institute ( NIH ) -Center for Cancer Research-National Institutes of Health, IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), St Jude Children's Research Hospital-University of Tennessee College of Medicine, Department of Pediatrics and Institute for Molecular Medicine Angello Nocivelli, University of Brescia, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Weller, Sandra, Università degli Studi di Brescia = University of Brescia (UniBs), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: MESH: Spleen, MESH: Antigens, CD27, MESH : Aged, MESH : Child, Preschool, Biochemistry, Immunoglobulin D, 0302 clinical medicine, MESH : Child, immune system diseases, MESH: Autoimmune Diseases, MESH: Child, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Child, Gene Rearrangement, B-Lymphocyte, MESH: Aged, 0303 health sciences, B-Lymphocytes, MESH: Middle Aged, biology, MESH: Gene Rearrangement, B-Lymphocyte, MESH: Immunoglobulin D, MESH : Infant, hemic and immune systems, Hematology, Middle Aged, MESH : Adult, Marginal zone, MESH: Infant, MESH: Immunoglobulin M, medicine.anatomical_structure, Child, Preschool, MESH : Immunophenotyping, Blood Circulation, MESH: Immunologic Memory, MESH: Complementarity Determining Regions, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Blood Circulation, Antibody, Adult, MESH : Spleen, MESH: Somatic Hypermutation, Immunoglobulin, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adolescent, MESH: Immunophenotyping, MESH : Immunologic Memory, MESH : Immunoglobulin M, Immunology, MESH : Somatic Hypermutation, Immunoglobulin, Somatic hypermutation, MESH : Complementarity Determining Regions, Spleen, chemical and pharmacologic phenomena, Article, MESH : Immunoglobulin D, Autoimmune Diseases, Immunophenotyping, MESH : B-Lymphocytes, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH : Autoimmune Diseases, MESH : Antigens, CD27, MESH : Adolescent, MESH: B-Lymphocytes, medicine, Humans, MESH : Middle Aged, 030304 developmental biology, Aged, MESH: Adolescent, MESH: Humans, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, MESH: Child, Preschool, Infant, MESH: Blood Circulation, MESH: Adult, Cell Biology, Gene rearrangement, Complementarity Determining Regions, Tumor Necrosis Factor Receptor Superfamily, Member 7, B-1 cell, Immunoglobulin M, MESH : Gene Rearrangement, B-Lymphocyte, biology.protein, Somatic Hypermutation, Immunoglobulin, Immunologic Memory, 030215 immunology
Abstract: International audience; The human peripheral B-cell compartment displays a large population of immunoglobulin M-positive, immunoglobulin D-positive CD27(+) (IgM(+)IgD(+)CD27(+)) "memory" B cells carrying a mutated immunoglobulin receptor. By means of phenotypic analysis, complementarity-determining region 3 (CDR3) spectratyping during a T-independent response, and gene-expression profiling of the different blood and splenic B-cell subsets, we show here that blood IgM(+)IgD(+)CD27(+) cells correspond to circulating splenic marginal zone B cells. Furthermore, analysis of this peripheral subset in healthy children younger than 2 years shows that these B cells develop and mutate their immunoglobulin receptor during ontogeny, prior to their differentiation into T-independent antigen-responsive cells. It is therefore proposed that these IgM(+)IgD(+)CD27(+) B cells provide the splenic marginal zone with a diversified and protective preimmune repertoire in charge of the responses against encapsulated bacteria.
Published: 2004
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27. Platelet-activating factor and normal or leukaemic haematopoiesis

Author: Laurence Guglielmi, Yves Denizot, Franck Trimoreau, Magali Donnard, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), and Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Signal Transduction, Cancer Research, B Cells, MESH : Receptors, Cell Surface, MESH: Hematopoiesis, Paf Receptor, MESH: Receptors, G-Protein-Coupled, Receptors, G-Protein-Coupled, chemistry.chemical_compound, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Receptor, MESH: Receptors, Cell Surface, B-Lymphocytes, Leukemia, Hematology, Leukaemic Diseases, Haematopoiesis, medicine.anatomical_structure, Oncology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Receptors, G-Protein-Coupled, lipids (amino acids, peptides, and proteins), Signal Transduction, Stromal cell, NLM, Receptors, Cell Surface, Blast Cells, Platelet Membrane Glycoproteins, Biology, MESH : B-Lymphocytes, Precursor cell, MESH: B-Lymphocytes, MESH: Leukemia, medicine, Humans, Progenitor cell, Platelet Activating Factor, B cell, MESH : Signal Transduction, MESH: Platelet Activating Factor, MESH: Humans, Platelet-activating factor, MESH : Humans, MESH : Leukemia, MESH: Platelet Membrane Glycoproteins, Hematopoiesis, MESH : Hematopoiesis, chemistry, MESH : Platelet Activating Factor, Immunology, Cancer research, Bone marrow, Platelet-activating Factor, MESH : Platelet Membrane Glycoproteins
Abstract: Platelet-activating factor (PAF), a phospholipid mediator with a wide range of actions on mature leukocytes, acts directly during early human haematopoiesis by affecting the growth of haematopoietic progenitors and indirectly, by modulating cytokine synthesis by bone marrow stromal cells. At this time, its role during leukaemic diseases remains speculative. The lack of membrane PAF receptor (PAF-R) on leukaemic blasts suggest that this receptor represents a marker of mature cells and its membrane induction a consequence of cell maturation. While the couple PAF/PAF-R has been largely studied using B cell lines, few results are available using B cells of patients with haematopoietic malignancies casting some doubts concerning the potential role (if any) of this molecule during leukaemic diseases.
Published: 2003
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28. Presence of membrane platelet-activating factor receptors on B cells of chronic B cell leukaemia patients

Author: Dominique Bordessoule, Magali Donnard, Franck Trimoreau, Arnaud Jaccard, Yves Denizot, Laurence Guglielmi, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Cancer Research, NLM, MESH : Male, MESH : Aged, MESH : Receptors, Cell Surface, Receptors, Cell Surface, MESH: Receptors, G-Protein-Coupled, Platelet Membrane Glycoproteins, Receptors, G-Protein-Coupled, MESH : B-Lymphocytes, chemistry.chemical_compound, MESH: B-Lymphocytes, medicine, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH : Middle Aged, Receptor, MESH: Leukemia, Lymphocytic, Chronic, B-Cell, B cell, MESH: Receptors, Cell Surface, Aged, MESH: Aged, B-Lymphocytes, MESH: Humans, MESH: Middle Aged, Platelet-activating factor, Chemistry, MESH : Humans, MESH: Platelet Membrane Glycoproteins, Hematology, Middle Aged, MESH : Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Molecular biology, MESH: Male, Membrane, medicine.anatomical_structure, Oncology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Receptors, G-Protein-Coupled, MESH: Female, MESH : Platelet Membrane Glycoproteins
Published: 2003
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29. Lymphocyte homeostasis

Author: Corinne Tanchot, Manuela M. Rosado, Fabien Agenes, Antonio A. Freitas, Benedita Rocha, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamiques Lymphocytaires, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH : Immunologic Memory, T-Lymphocytes, Immunology, Bone Marrow Cells, Thymus Gland, MESH : Models, Immunological, Lymphocyte Activation, MESH: Models, Immunological, MESH : B-Lymphocytes, 03 medical and health sciences, Mice, 0302 clinical medicine, MESH: B-Lymphocytes, MESH : Mice, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Animals, Homeostasis, MESH : Thymus Gland, MESH: Animals, MESH: Lymphocyte Activation, MESH: Mice, MESH : Lymphocyte Activation, 030304 developmental biology, MESH : T-Lymphocytes, 0303 health sciences, B-Lymphocytes, MESH: Bone Marrow Cells, Models, Immunological, MESH: Thymus Gland, MESH: T-Lymphocytes, MESH: Homeostasis, MESH : Homeostasis, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Animals, Immunologic Memory, MESH : Bone Marrow Cells, 030215 immunology
Abstract: International audience; B- and T-lymphocyte populations have an independent homeostatic regulation of resting (B and T) and activated (B) or memory (T) cell compartments. This organization may provide an efficient mechanism to ensure simultaneously a first natural barrier of protection against common pathogens, the maintenance of immunological T-cell memory and a reservoir of repertoire diversity capable of dealing with new antigenic challenges.
Published: 1997
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29 results on '"MESH : B-Lymphocytes"'

1. Candida albicans is able to use M cells as a portal of entry across the intestinal barrier in vitro

2. Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor

3. CD40 Ligand Protects from TRAIL-Induced Apoptosis in Follicular Lymphomas through NF-κB Activation and Up-Regulation of c-FLIP and Bcl-xL

4. The human spleen is a major reservoir for long-lived vaccinia virus–specific memory B cells

5. DNA polymerases in adaptive immunity. : DNA polymerases in adaptive immunity

6. Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+IgD+CD27+ B cell repertoire in infants

7. Quantitative analysis of inflammatory cells infiltrating the cystic fibrosis airway mucosa

8. Persistence of natural killer cells with expansion of a hypofunctional CD56-CD16+KIR+NKG2C+ subset in a patient with atypical Janus kinase 3-deficient severe combined immunodeficiency

9. Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort

10. Multifocal polyclonal Epstein-Barr virus-associated B-cell lymphoproliferative disorder secondary to azathioprine therapy successfully treated with rituximab

11. Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg cells and normal B-lymphocytes

12. Stepwise development of MAIT cells in mouse and human

13. Role of regulatory T cells in a new mouse model of experimental autoimmune myositis

14. Tetrameric and homodimeric camelid IgGs originate from the same IgH locus

15. Cell surface expression of the bovine leukemia virus-binding receptor on B and T lymphocytes is induced by receptor engagement

16. Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cells

17. Lentiviral transduction of immune cells

18. Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patients

19. Pathophysiological aspects of memory B-cell development

20. Role for DNA repair factor XRCC4 in immunoglobulin class switch recombination

21. The SH2 domain-containing inositol 5-phosphatase SHIP1 is recruited to the intracytoplasmic domain of human FcgammaRIIB and is mandatory for negative regulation of B cell activation

22. Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study

23. Dynamics of thymus-colonizing cells during human development

24. In vitro functional defects of bone marrow-derived CD34+ progenitors from newly diagnosed mature B-cell malignancies with bone marrow tumor involvement

25. Normal immune system development in mice lacking the Deltex-1 RING finger domain

26. Human blood IgM 'memory' B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire

27. Platelet-activating factor and normal or leukaemic haematopoiesis

28. Presence of membrane platelet-activating factor receptors on B cells of chronic B cell leukaemia patients

29. Lymphocyte homeostasis

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29 results on '"MESH : B-Lymphocytes"'

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