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Your search keyword '"Bruno Iannascoli"' showing total 10 results
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10 results on '"Bruno Iannascoli"'

1. High-throughput single-cell activity-based screening and sequencing of antibodies using droplet microfluidics

Author

Andrew D. Griffiths, Alexei Godina, Guillaume Mottet, Gaël A. Millot, Bingqing Shen, Samantha N. Stewart, Vera Menrath, Sosthene Essono, Baptiste Saudemont, Clément Nizak, Annabelle Gérard, Antoine Sautel-Caillé, Scott McNamara, Matthieu Delince, Sami Ellouze, Jean Baudry, Marcel Reichen, Pablo Canales-Herrerias, Charina Ortega, Patrick England, Carlos Castrillon, Odile Richard-Le Goff, Colin Brenan, Klaus Eyer, Pascaline Mary, Luis Briseño-Roa, Allan Jensen, Pierre Bruhns, Raphael Clement Li-Ming Doineau, Adam Woolfe, Roshan Kumar, Bin Jia, Bruno Iannascoli, Yannick Pousse, Kevin Grosselin, Gregory Rose, Adeline Poitou, HiFiBiO Therapeutics SAS [Paris], Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Doctorale Frontières du Vivant - Programme Bettencourt (FdV), Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité, Chimie-Biologie-Innovation (UMR 8231) (CBI), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Colloïdes et Matériaux Divisés (LCMD), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), HiFiBiO Therapeutics Inc. [Cambridge], Abbvie Bioresearch Center [Worcester], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biophysique Moléculaire (Plate-forme), Biophysique des macromolécules et leurs interactions, This work was supported by the French Agence Nationale de la Recherche (ANR-14-CE16-0011 project DROPmAbs), by the Centre d’Innovation et Recherche Technologique (Citech) through the Institut Carnot Pasteur Microbes & Santé (ANR 16 CARN 0023-01), by BPI France (OSIRIS and CELLIGO projects) and by the French ‘Investissements d’Avenir’ program via the CELLIGO project and grant agreements ANR-10-NANO-02, ANR-10-IDEX-0001-02 PSL, ANR-10-LABX-31 and ANR-10-EQPX-34. NGS was performed by the ICGex NGS platform of the Institut Curie and the Institut de Biologie Intégrative de la Cellule (I2BC) platform (Gif-sur-Yvette) supported by the grants ANR-10-EQPX-03 and ANR-10-INBS-09-08 (France Génomique Consortium), by the Canceropole Ile-de-France and by the SiRIC-Curie program (SiRIC Grant INCa-DGOS- 4654). C.C. acknowledges financial support from CONCYTEC, Peru. P.C.H. is a scholar in the Pasteur - Paris University (PPU) International PhD program and was also supported by the Fondation pour la Recherche Médicale (FRM, FDT201904008240). K.E. acknowledges financial support from the Swiss National Science Foundation and The Branco Weiss Fellowship - Society in Science., We would like to thank M. Holsti and W. Somers (Pfizer, BioMedicine Design) for advice on the technology development and critical reading of the manuscript, R. Nicol (Whitehead Institute, MIT Center for Genome Research) for advice on barcoded sequencing, at the Institut Pasteur, H. Mouquet for advice on antibody sequence selection, and F. Jönsson for advice on flow cytometry analysis, T. Kirk and S. Foulon (ESPCI Paris) for their help developing the barcoded hydrogel beads, S. N. Stewart (HiFiBio Therapeutics Inc.) for her help producing and analysing recombinant antibodies, the Institut Pierre-Gilles de Gennes (IPGG) for use of clean room facilities and the laser engraver (CII08, Axyslaser)., ANR-14-CE16-0011,DROP-mAbs,Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques(2014), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-10-EQPX-0034,IPGG,Institut Pierre Gilles de Gennes pour la microfluidique(2010), ANR-10-EQPX-0003,ICGex,Equipement de biologie intégrative du cancer pour une médecine personnalisée(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Bruhns, Pierre, Appel à projets générique - Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques - - DROP-mAbs2014 - ANR-14-CE16-0011 - Appel à projets générique - VALID, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Equipements d'excellence - Institut Pierre Gilles de Gennes pour la microfluidique - - IPGG2010 - ANR-10-EQPX-0034 - EQPX - VALID, Equipements d'excellence - Equipement de biologie intégrative du cancer pour une médecine personnalisée - - ICGex2010 - ANR-10-EQPX-0003 - EQPX - VALID, and Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, Biomedical Engineering, Somatic hypermutation, Bioengineering, Cancer Vaccines, Applied Microbiology and Biotechnology, Antibodies, Mice, 03 medical and health sciences, 0302 clinical medicine, Antibody Repertoire, Antigen, Animals, Humans, Antigens, 030304 developmental biology, chemistry.chemical_classification, B-Lymphocytes, 0303 health sciences, biology, High-Throughput Nucleotide Sequencing, DNA, Microfluidic Analytical Techniques, Molecular biology, Reverse transcriptase, 3. Good health, Enzyme, chemistry, Immunization, Immunoglobulin G, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Medicine, Single-Cell Analysis, Antibody, 030217 neurology & neurosurgery, Ex vivo, Biotechnology
Abstract

International audience; Mining the antibody repertoire of plasma cells and plasmablasts could enable the discovery of useful antibodies for therapeutic or research purposes1. We present a method for high-throughput, single-cell screening of IgG-secreting primary cells to characterize antibody binding to soluble and membrane-bound antigens. CelliGO is a droplet microfluidics system that combines high-throughput screening for IgG activity, using fluorescence-based in-droplet single-cell bioassays2, with sequencing of paired antibody V genes, using in-droplet single-cell barcoded reverse transcription. We analyzed IgG repertoire diversity, clonal expansion and somatic hypermutation in cells from mice immunized with a vaccine target, a multifunctional enzyme or a membrane-bound cancer target. Immunization with these antigens yielded 100–1,000 IgG sequences per mouse. We generated 77 recombinant antibodies from the identified sequences and found that 93% recognized the soluble antigen and 14% the membrane antigen. The platform also allowed recovery of ~450–900 IgG sequences from ~2,200 IgG-secreting activated human memory B cells, activated ex vivo, demonstrating its versatility.

Published
2020

2. The anti-IgE mAb omalizumab induces adverse reactions by engaging Fcγ receptors

Author

Bianca Balbino, Julien Stackowicz, Kari C. Nadeau, Pauline Herviou, Ophélie Godon, Sébastien Brûlé, Delphine Sterlin, Andrew J. Murphy, Vera Voronina, Bruno Iannascoli, Odile Richard-Le Goff, Gaël A. Millot, Macdonald Lynn, Laurent L. Reber, Harris Faith, Pierre Bruhns, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biophysique Moléculaire (Plate-forme), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Regeneron Pharmaceuticals [Tarrytown], Stanford University, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Commission (Marie Skłodowska-Curie Individual Fellowship H2020-MSCA-IF-2014 656086)European 235Research Council (ERC)–Seventh Framework Program (ERC-2013-CoG 616050)Institut Pasteur initiative for valorizing the applications of research (ValoExpress 2017)INSERM, ATIP-Avenir program'Investissement d’Avenir'(grant ANR-11-INBS-0006)Pasteur -Paris University (PPU) International Ph.DprogramFrench 'Fondation pour la Recherche Médicale FRMAP-HP, ANR-11-INBS-0006,FLI,France Life Imaging(2011), European Project: 616050,EC:FP7:ERC,ERC-2013-CoG,MYELOSHOCK(2014), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and 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)

Subjects
0301 basic medicine, Allergy, MESH: Asthma / immunology, Omalizumab, MESH: Anaphylaxis / immunology, Immunoglobulin E, MESH: Mice, Knockout, Mice, MESH: Asthma / pathology, 0302 clinical medicine, Medicine, MESH: Animals, MESH: Drug Eruptions / pathology, Mice, Knockout, biology, Concise Communication, General Medicine, MESH: Drug Eruptions / genetics, 3. Good health, MESH: Anaphylaxis / pathology, MESH: Omalizumab / genetics, 030220 oncology & carcinogenesis, MESH: Drug Eruptions / immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Eruptions, Antibody, medicine.symptom, Anaphylaxis, medicine.drug, MESH: Mutation, MESH: Anaphylaxis / chemically induced, medicine.drug_class, Immunology, Immunoglobulins, Inflammation, Monoclonal antibody, MESH: Receptors, IgG / immunology, 03 medical and health sciences, Immune system, MESH: Omalizumab / adverse effects, Animals, MESH: Receptors, IgG / genetics, MESH: Mice, MESH: Omalizumab / pharmacology, business.industry, Receptors, IgG, MESH: Asthma / drug therapy, medicine.disease, Asthma, 030104 developmental biology, Mutation, Mast cells, MESH: Anaphylaxis / genetics, biology.protein, business
Abstract

International audience; Omalizumab is an anti-IgE monoclonal antibody (mAb) approved for the treatment of severe asthma and chronic spontaneous urticaria. Use of Omalizumab is associated with reported side effects, ranging from local skin inflammation at the injection site to systemic anaphylaxis. To date, the mechanisms through which Omalizumab induces adverse reactions are still unknown. Here, we demonstrated that immune complexes formed between Omalizumab and IgE can induce both skin inflammation and anaphylaxis through engagement of IgG receptors (FcγRs) in FcγR-humanized mice. We further developed an Fc-engineered mutant version of Omalizumab, and demonstrated that this mAb is equally potent as Omalizumab at blocking IgE-mediated allergic reactions, but does not induce FcγR-dependent adverse reactions. Overall, our data indicate that Omalizumab can induce skin inflammation and anaphylaxis by engaging FcγRs, and demonstrate that Fc-engineered versions of the mAb could be used to reduce such adverse reactions.

Published
2020

3. High-affinity autoreactive plasma cells disseminate through multiple organs in patients with immune thrombocytopenic purpura

Author

Pablo Canales-Herrerias, Etienne Crickx, Matteo Broketa, Aurélien Sokal, Guilhem Chenon, Imane Azzaoui, Alexis Vandenberghe, Angga Perima, Bruno Iannascoli, Odile Richard-Le Goff, Carlos Castrillon, Guillaume Mottet, Delphine Sterlin, Ailsa Robbins, Marc Michel, Patrick England, Gael A. Millot, Klaus Eyer, Jean Baudry, Matthieu Mahevas, Pierre Bruhns, RICHARD-LE GOFF, ODILE, APPEL À PROJETS GÉNÉRIQUE 2018 - Etude de la rupture de tolérance dans une maladie humaine autoimmune médiée par les lymphocytes B - - Autoimmuni-B2018 - ANR-18-CE15-0001 - AAPG2018 - VALID, Appel à projets générique - Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques - - DROP-mAbs2014 - ANR-14-CE16-0011 - Appel à projets générique - VALID, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Equipements d'excellence - Institut Pierre Gilles de Gennes pour la microfluidique - - IPGG2010 - ANR-10-EQPX-0034 - EQPX - VALID, Laboratoire Colloïdes et Matériaux Divisés (LCMD), Chimie-Biologie-Innovation (UMR 8231) (CBI), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Ecole Doctorale Frontières du Vivant - Programme Bettencourt (FdV), Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de référence maladie rare des cytopénies auto-immunes de l'adulte (GECAI - Hôpital Henri-Mondor - UPEC), Diaccurate SAS, Physiologie, physiopathologie et thérapeutique (ED 394), Sorbonne Université (SU), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Henri Mondor, Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), P.C-H. was supported partly by a stipend from the Pasteur - Paris University (PPU) InternationalPhD program, and by a fellowship from the French Fondation pour la Recherche Médicale (FRM). M.B.is the recipient of a CIFRE PhD fellowship. C.C. was supported by CONCYTEC, Peru. P.B. acknowledgesfunding from the French National Research Agency grants ANR-18-CE15-0001 project Autoimmuni-Band ANR-14-CE16-0011 project DROPmAbs, funding by the Institut Carnot Pasteur Microbes et Santé,the Institut Pasteur and the Institut National de la Santé et de la Recherche Médicale (INSERM). E.K.acknowledges funding from the Branco Weiss Fellowship (Society in Science) and the European ResearchCouncil (ERC) (grant agreement #80336). J.B. acknowledges funding from the French government throughBPIFrance under the frame 'Programme d’Investissements d’Avenir' (CELLIGO Project), the 'InstitutPierre-Gilles de Gennes' through the laboratoire d’excellence, 'Investissements d’avenir' programs ANR-10-IDEX-0001-02 PSL, ANR-10- EQPX-34 and ANR-10-LABX-3, The authors acknowledge Ms Laetitia Languille for the coordination of patient recruitment at Hôpital Henri Mondor, Créteil, France, Dr Maxime Moulard (BioCytex, Marseille, France) and Dr Habib Boukerche (Faculté de Médecine René Laënnec, Lyon, France) for their kind gifts of anti-αIIbβ3 (GPIIbIIIa) mAb clones., ANR-18-CE15-0001,Autoimmuni-B,Etude de la rupture de tolérance dans une maladie humaine autoimmune médiée par les lymphocytes B(2018), ANR-14-CE16-0011,DROP-mAbs,Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques(2014), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-10-EQPX-0034,IPGG,Institut Pierre Gilles de Gennes pour la microfluidique(2010), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Université Paris Cité (UPCité), and CHU Henri Mondor [Créteil]

Subjects
Blood Platelets, Platelets, Purpura, Thrombocytopenic, Idiopathic, [SDV.IMM] Life Sciences [q-bio]/Immunology, Autoimmune diseases, Plasma Cells, Adaptive immunity, Autoimmunity, General Medicine, Therapeutics, Immunoglobulin G, hemic and lymphatic diseases, Splenectomy, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Autoantibodies
Abstract

The major therapeutic goal for immune thrombocytopenic purpura (ITP) is to restore normal platelet counts using drugs to promote platelet production or by interfering with mechanisms responsible for platelet destruction. Eighty percent of patients with ITP possess anti???integrin ??IIb??3 IgG autoantibodies that cause platelet opsonization and phagocytosis. The spleen is considered the primary site of autoantibody production by autoreactive B cells and platelet destruction. The immediate failure in approximately 50% of patients to recover a normal platelet count after anti-CD20 rituximab-mediated B cell depletion and splenectomy suggests that autoreactive, rituximab-resistant, IgG-secreting B cells (IgG-SCs) reside in other anatomical compartments. We analyzed more than 3,300 single IgG-SCs from spleen, bone marrow, and/or blood of 27 patients with ITP, revealing high interindividual variability in affinity for ??IIb??3, with variations over 3 logs. IgG-SC dissemination and range of affinities were, however, similar for each patient. Longitudinal analysis of autoreactive IgG-SCs upon treatment with the anti-CD38 mAb daratumumab demonstrated variable outcomes, from complete remission to failure with persistence of high-affinity anti?????IIb??3 IgG-SCs in the bone marrow. This study demonstrates the existence and dissemination of high-affinity autoreactive plasma cells in multiple anatomical compartments of patients with ITP that may cause the failure of current therapies., The Journal of Clinical Investigation, 132 (12), ISSN:1558-8238, ISSN:0021-9738

Published
2022

4. Specificity of mouse and human Fcgamma receptors and their polymorphic variants for IgG subclasses of different species

Author

Yu Wang, Vanessa Krémer, Bruno Iannascoli, Odile Richard‐Le Goff, David A. Mancardi, Leoni Ramke, Luc Chaisemartin, Pierre Bruhns, Friederike Jönsson, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS), This work was supported by a Jeunes Chercheuses/Jeunes Chercheurs grant from the Agence National de la Recherche (ANR- 16-CE15-0012), Institut National de la Recherche Médicale (INSERM) and Institut Pasteur. YW and VK are part of the Pasteur–Paris University (PPU) International PhD Program. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 665807, and from the Labex Milieu Intérieur, Institut Pasteur. For the purpose of open access, the author has applied a CC BY public copyright license to any author accepted manuscript version arising from this submission., ANR-16-CE15-0012,PlanA,Rôle des plaquettes et leurs interactions dans les réactions anaphylactiques(2016), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), Jönsson, Friederike, Rôle des plaquettes et leurs interactions dans les réactions anaphylactiques - - PlanA2016 - ANR-16-CE15-0012 - AAPG2016 - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, and Institut Pasteur International Docotal Program - PASTEURDOC - - H20202015-10-01 - 2020-10-01 - 665807 - VALID

Subjects
Hybridomas, [SDV.IMM] Life Sciences [q-bio]/Immunology, Fcγ receptors, cross-binding, IgG, Receptors, IgG, Immunology, Mice, Transgenic, 3. Good health, immune complexes, Mice, Immunoglobulin G, Animals, Humans, Immunology and Allergy, [SDV.IMM]Life Sciences [q-bio]/Immunology, Carrier Proteins
Abstract

International audience; Immunoglobulin G (IgG) is the predominant antibody class generated during infections and used for the generation of therapeutic antibodies. Antibodies are mainly characterized in or generated from animal models that support particular infections, respond to particular antigens or allow the generation of hybridomas. Due to the availability of numerous transgenic mouse models and the ease of performing bioassays with human blood cells in vitro, most antibodies from species other than mice and humans are tested in vitro using human cells and/or in vivo using mice. In this process, it is expected, but not yet systematically documented, that IgG from these species interact with human or mouse IgG receptors (FcRs). In this study, we undertook a systematic assessment of binding specificities of IgG from various species to the families of mouse and human FcRs, including their polymorphic variants. Our results document the specific binding patterns for each of these IgG (sub)classes, reveal possible caveats of antibody-based immunoassays, and will be a useful reference for the transition from one animal model to preclinical mouse models or human cell-based bioassays.

Published
2022

5. Neutrophils mediate antibody-induced antitumor effects in mice

Author

James P. Di Santo, Pierre Bruhns, Laurence Fiette, Friederike Jönsson, David A. Mancardi, Clifford A. Lowell, Bruno Iannascoli, Marcello Albanesi, Anticorps en Thérapie et Pathologie, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Immunité Innée, University of California [San Francisco] (UCSF), University of California, This work was supported by the Institut Pasteur and the Institut National de la Santé et de la Recherche Médicale, by Agence Nationale de la Recherche (grant ANR-09-GENO-014-01), Fondation ARC pour la Recherche sur le Cancer and Ligue Nationale contre le Cancer (Comité de Paris) grants (P.B.), through an 'Equipe Labellisée Ligue Contre le Cancer' grant (J.P.D.S.), and by National Institutes of Health, National Institute of Allergy and Infectious Diseases grants AI065495 and AI068150 (C.A.L.)., The authors are thankful to our colleagues at Institut Pasteur (Paris, France): P. Bousso (Dynamics of Immune Responses Unit) for discussions and advice, M.-A. Nicola (Plate-Forme d'Imagerie Dynamique) for help with bioluminescence experiments, X. Montagutelli, Q. Mille, D. Montean, and G. Labas for help with mouse colony management (Central Animal Facility), C. Detchepare and C. Nizak for administrative help (Laboratoire Anticorps en Thérapie et Pathologie), and at University of California, San Francisco (San Francisco, CA): Y. Hu for animal husbandry. The authors are grateful to their colleagues for providing mice or reagents: R. Coffman (DNAX, Palo Alto, CA), B. Hann (University of California, San Francisco), J. J. Lee (Mayo Clinic, Scottsdale, AZ), H. Karasuyama (Tokyo Medical and Dental University Graduate School, Tokyo, Japan), M.P. Reilly (Jefferson Medical College, Philadelphia, PA), and M. Tarik (Montreal University, Montreal, QC, Canada)., ANR-09-GENO-0014,InflammAbs,Contrôle de l'inflammation par les RFc humains dans des modèles murins d'allergie et d'autoimmunité.(2009), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), University of California [San Francisco] (UC San Francisco), University of California (UC), Martin, Marie, and Physiopathologie moléculaire: des maladies rares aux maladies communes - Contrôle de l'inflammation par les RFc humains dans des modèles murins d'allergie et d'autoimmunité. - - InflammAbs2009 - ANR-09-GENO-0014 - GENO - VALID

Subjects
MESH: Tumor Burden, Neutrophils, medicine.medical_treatment, Melanoma, Experimental, MESH: Neutrophils, MESH: Mice, Knockout, Biochemistry, Immunoglobulin G, MESH: Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, Mice, 0302 clinical medicine, Conditional gene knockout, MESH: Animals, MESH: Trastuzumab, Mice, Knockout, 0303 health sciences, biology, Melanoma, Antibodies, Monoclonal, Hematology, Tumor Burden, 3. Good health, MESH: Melanoma, Experimental, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Rituximab, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Antibody, Rituximab, MESH: Xenograft Model Antitumor Assays, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Transgenic, medicine.drug_class, Immunology, Mice, Nude, Breast Neoplasms, Mice, Transgenic, MESH: Receptors, IgG, Antibodies, Monoclonal, Humanized, Monoclonal antibody, 03 medical and health sciences, Antigen, MESH: Mice, Inbred C57BL, Cell Line, Tumor, MESH: Mice, Nude, MESH: Antibody-Dependent Cell Cytotoxicity, medicine, Animals, Humans, MESH: Mice, 030304 developmental biology, MESH: Humans, Receptors, IgG, Antibody-Dependent Cell Cytotoxicity, Cancer, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Cell Biology, Immunotherapy, Trastuzumab, medicine.disease, Xenograft Model Antitumor Assays, Mice, Inbred C57BL, MESH: Antibodies, Monoclonal, Humanized, MESH: Antibodies, Monoclonal, Murine-Derived, biology.protein, MESH: Breast Neoplasms
Abstract

International audience; Tumor engraftment followed by monoclonal antibody (mAb) therapy targeting tumor antigens represents a gold standard for assessing the efficiency of mAbs to eliminate tumor cells. Mouse models have demonstrated that receptors for the Fc portion of immunoglobulin G (FcγRs) are critical determinants of mAb therapeutic efficacy, but the FcγR-expressing cell populations responsible remain elusive. We show that neutrophils are responsible for mAb-induced therapy of both subcutaneous syngeneic melanoma and human breast cancer xenografts. mAb-induced tumor reduction, abolished in neutropenic mice, could be restored in FcγR-deficient hosts upon transfer of FcγR+ neutrophils or upon human FcγRIIA/CD32A transgenic expression. Finally, conditional knockout mice unable to perform FcγR-mediated activation and phagocytosis specifically in neutrophils were resistant to mAb-induced therapy. Our work suggests that neutrophils are necessary and sufficient for mAb-induced therapy of subcutaneous tumors, and represent a new and critical focal point for optimizing mAb-induced immunotherapies that will impact on human cancer treatment.

Published
2013

6. Cutting Edge: FcγRIII (CD16) and FcγRI (CD64) Are Responsible for Anti-Glycoprotein 75 Monoclonal Antibody TA99 Therapy for Experimental Metastatic B16 Melanoma

Author

Pierre Bruhns, Andrew J. Murphy, Marcello Albanesi, Laurence Zitvogel, Jeanette H. W. Leusen, Bruno Iannascoli, David A. Mancardi, Macdonald Lynn, Anticorps en Thérapie et Pathologie, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Allergologie Moléculaire et Cellulaire, Regeneron Pharmaceuticals [Tarrytown], Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), University Medical Center [Utrecht], This work was supported by the Institut Pasteur, the INSERM, the Agence Nationale de la Recherche (Grant 09-GENO-014-01), the Fondation Association pour la Recherche sur le Cancer, and the Ligue Nationale contre le Cancer (Comité de Paris). M.A. is a scholar from the Pasteur Paris University International Doctoral Program., ANR-09-GENO-0014,InflammAbs,Contrôle de l'inflammation par les RFc humains dans des modèles murins d'allergie et d'autoimmunité.(2009), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Lung Neoplasms, Cyclophosphamide, Combination therapy, medicine.drug_class, MESH: Hybridomas, Immunology, Melanoma, Experimental, MESH: Receptors, IgG, CD16, Monoclonal antibody, MESH: Mice, Knockout, MESH: Antibodies, Monoclonal, Mice, Viral Proteins, 03 medical and health sciences, 0302 clinical medicine, MESH: Mice, Inbred C57BL, MESH: Arboviruses, MESH: Antibodies, Blocking, medicine, Animals, Immunology and Allergy, MESH: Animals, Antibodies, Blocking, MESH: Mice, 030304 developmental biology, Mice, Knockout, CD64, chemistry.chemical_classification, 0303 health sciences, Hybridomas, business.industry, Receptors, IgG, Antibodies, Monoclonal, MESH: Viral Proteins, MESH: Lung Neoplasms, 3. Good health, Mice, Inbred C57BL, MESH: Melanoma, Experimental, chemistry, Tumor reduction, [SDV.IMM]Life Sciences [q-bio]/Immunology, Glycoprotein, business, Arboviruses, B16 melanoma, 030215 immunology, medicine.drug
Abstract

Erratum in J Immunol. 2013 Feb 1;190(3):1381. Daëron, Marc [added].; International audience; mAb therapy for experimental metastatic melanoma relies on activating receptors for the Fc portion of IgG (FcγR). Opposing results on the respective contribution of mouse FcγRI, FcγRIII, and FcγRIV have been reported using the gp75-expressing B16 melanoma and the protective anti-gp75 mAb TA99. We analyzed the contribution of FcγRs to this therapy model using bioluminescent measurement of lung metastases loads, novel mouse strains, and anti-FcγR blocking mAbs. We found that the TA99 mAb-mediated effects in a combination therapy using cyclophosphamide relied on activating FcγRs. The combination therapy, however, was not more efficient than mAb therapy alone. We demonstrate that FcγRI and, unexpectedly, FcγRIII contributed to TA99 mAb therapeutic effects, whereas FcγRIV did not. Therefore, FcγRIII and FcγRI are, together, responsible for anti-gp75 mAb therapy of B16 lung metastases. Our finding that mouse FcγRIII contributes to Ab-induced tumor reduction correlates with clinical data on its human functional equivalent human FcγRIIIA (CD16A).

Published
2012

7. IgG subclasses determine pathways of anaphylaxis in mice

Author

Mark S. Cragg, Caitlin M. Gillis, Patrick England, Nico van Rooijen, Héloïse Beutier, Stephen J. Galli, Riccardo Sibilano, Laurent L. Reber, Pierre Bruhns, Friederike Jönsson, Bruno Iannascoli, Ophélie Godon, David A. Mancardi, Université Pierre et Marie Curie - Paris 6 (UPMC), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique Moléculaire (Plate-forme), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, University of Southampton, VU University Medical Center [Amsterdam], We thank our colleagues at Institut Pasteur, Paris: D. Sinnaya for administrative help, Stéphane Petres for help with antibody purifications, and Laurence Fiette for help with histological analyses. We thank our colleagues for their generous gifts: T. Moroy (Montreal University, Montreal, Quebec, Canada), C. Lowell (University of California at San Francisco, San Francisco, Calif), J. V. Ravetch (Rockefeller University, New York, NY, USA), and J. Leusen (University Medical Center, Utrecht, The Netherlands) for mice and R. Coffman (DNAX, Palo Alto, Calif), R. Good (USFCM, Tampa, Fla), B. Heyman (Uppsala Universitet, Uppsala, Sweden), H. Karasuyama (Tokyo Medical and Dental University Graduate School, Tokyo, Japan), and D. Voehringer (Universitätsklinikum, Erlangen, Germany) for antibodies. Cl2MDP was a gift of Roche Diagnostics GmbH., Bidault, Floran, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Allergy, Basophil, chemistry.chemical_compound, basophil, 0302 clinical medicine, Immunology and Allergy, Macrophage, Myeloid Cells, Receptor, Chemistry, Antibodies, Monoclonal, neutrophil, Serum Albumin, Bovine, hemic and immune systems, 3. Good health, medicine.anatomical_structure, 1107 Immunology, monocyte, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Anaphylaxis, Histamine, platelet-activating factor, [SDV.IMM] Life Sciences [q-bio]/Immunology, IgG, mouse model, Immunology, Mice, Transgenic, chemical and pharmacologic phenomena, IgG Fc receptor, macrophage, Article, 03 medical and health sciences, Downregulation and upregulation, medicine, Animals, Platelet-activating factor, Monocyte, Receptors, IgG, Immunoglobulin E, medicine.disease, histamine, Mice, Inbred C57BL, Protein Subunits, 030104 developmental biology, Immunoglobulin G, Haptens, 030215 immunology
Abstract

Background: Animal models have demonstrated that allergen-specific IgG confers sensitivity to systemic anaphylaxis that relies on IgG Fc receptors (Fc?Rs). Mouse IgG2a and IgG2b bind activating Fc?RI, Fc?RIII, and Fc?RIV and inhibitory Fc?RIIB; mouse IgG1 binds only Fc?RIII and Fc?RIIB. Although these interactions are of strikingly different affinities, these 3 IgG subclasses have been shown to enable induction of systemic anaphylaxis.Objective: We sought to determine which pathways control the induction of IgG1-, IgG2a-, and IgG2b-dependent passive systemic anaphylaxis.Methods: Mice were sensitized with IgG1, IgG2a, or IgG2b anti-trinitrophenyl mAbs and challenged with trinitrophenyl-BSA intravenously to induce systemic anaphylaxis that was monitored by using rectal temperature. Anaphylaxis was evaluated in mice deficient for Fc?Rs injected with mediator antagonists or in which basophils, monocytes/macrophages, or neutrophils had been depleted. Fc?R expression was evaluated on these cells before and after anaphylaxis.Results: Activating Fc?RIII is the receptor primarily responsible for all 3 models of anaphylaxis, and subsequent downregulation of this receptor was observed. These models differentially relied on histamine release and the contribution of mast cells, basophils, macrophages, and neutrophils. Strikingly, basophil contribution and histamine predominance in mice with IgG1- and IgG2b-induced anaphylaxis correlated with the ability of inhibitory Fc?RIIB to negatively regulate these models of anaphylaxis.Conclusion: We propose that the differential expression of inhibitory Fc?RIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass–dependent anaphylaxis. Collectively, our results unravel novel complexities in the involvement and regulation of cell populations in IgG-dependent reactions in vivo.

Published
2016

8. Human FcγRIIA induces anaphylactic and allergic reactions

Author

Nico van Rooijen, Friederike Jönsson, Lawrence B. Schwartz, Takao Shimizu, Wei Zhao, Marc Daëron, David A. Mancardi, Yoshihiro Kita, Bruno Iannascoli, Pierre Bruhns, Huot Khun, Allergologie Moléculaire et Cellulaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Virginia Commonwealth University (VCU), The University of Tokyo (UTokyo), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Department of Molecular Cell Biology [Amsterdam UMC], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU)-Vrije Universiteit Amsterdam [Amsterdam] (VU), This work was supported by the Institut Pasteur, Inserm, the Agence Nationale de la Recherche (ANR, grant GENOPAT-09-GENO-014-01), the Société Française d'Allergologie (SFA, Soutien de la recherche en allergologie 2010), and the Balsan company. F.J. is a recipient of a fellowship from the Fondation pour la Recherche Médicale (FRM). D.A.M. is a recipient of a fellowship from the Institut Pasteur (Bourse Roux). W.Z. and L.B.S. were funded in part by U19AI077435 from the National Institutes of Health., ANR-09-GENO-0014,InflammAbs,Contrôle de l'inflammation par les RFc humains dans des modèles murins d'allergie et d'autoimmunité.(2009), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Molecular cell biology and Immunology, and CCA - Immuno-pathogenesis

Subjects
MESH: Inflammation, Allergy, Respiratory System, mast cells, airway inflammation, MESH: Neutrophils, Immunoglobulin E, MESH: Mice, Knockout, Biochemistry, 0302 clinical medicine, neutrophils, MESH: Animals, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Receptor, Cells, Cultured, MESH: Respiratory System, Mice, Knockout, 0303 health sciences, biology, Passive Cutaneous Anaphylaxis, Airway inflammation, MESH: Mast Cells, Hematology, immunoglobulin e, macrophages, 3. Good health, immunoglobulin g, [SDV.IMM]Life Sciences [q-bio]/Immunology, hypersensitivity, monocytes, MESH: Passive Cutaneous Anaphylaxis, MESH: Cells, Cultured, mice, MESH: Mice, Transgenic, MESH: Hypersensitivity, Immunology, Mice, Transgenic, MESH: Receptors, IgG, 03 medical and health sciences, MESH: Eosinophils, MESH: Mice, Inbred C57BL, In vivo, anaphylaxis, medicine, Animals, Humans, MESH: Mice, 030304 developmental biology, Inflammation, MESH: Humans, Passive anaphylaxis, business.industry, Receptors, IgG, Anaphylactic reactions, Cell Biology, medicine.disease, Eosinophils, Mice, Inbred C57BL, biology.protein, business, 030215 immunology
Abstract

IgE and IgE receptors (FcϵRI) are well-known inducers of allergy. We recently found in mice that active systemic anaphylaxis depends on IgG and IgG receptors (FcγRIIIA and FcγRIV) expressed by neutrophils, rather than on IgE and FcϵRI expressed by mast cells and basophils. In humans, neutrophils, mast cells, basophils, and eosinophils do not express FcγRIIIA or FcγRIV, but FcγRIIA. We therefore investigated the possible role of FcγRIIA in allergy by generating novel FcγRIIA-transgenic mice, in which various models of allergic reactions induced by IgG could be studied. In mice, FcγRIIA was sufficient to trigger active and passive anaphylaxis, and airway inflammation in vivo. Blocking FcγRIIA in vivo abolished these reactions. We identified mast cells to be responsible for FcγRIIA-dependent passive cutaneous anaphylaxis, and monocytes/macrophages and neutrophils to be responsible for FcγRIIA-dependent passive systemic anaphylaxis. Supporting these findings, human mast cells, monocytes and neutrophils produced anaphylactogenic mediators after FcγRIIA engagement. IgG and FcγRIIA may therefore contribute to allergic and anaphylactic reactions in humans.

Published
2012

9. Peritoneal Cell-Derived Mast Cells: An In Vitro Model of Mature Serosal-Type Mouse Mast Cells

Author

Michel Arock, Antoine Ribadeau Dumas, Marc Daëron, Karine Roget, Bruno Iannascoli, Cécile Schiffer, Odile Malbec, Allergologie Moléculaire et Cellulaire, Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut Pasteur [Paris]-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 Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Chemokine, MESH : Phosphoric Monoester Hydrolases, Cellular differentiation, Cell, Cell Count, MESH : Cell Count, MESH : Models, Immunological, Immunoglobulin E, MESH: Mice, Knockout, MESH: Down-Regulation, MESH : Down-Regulation, Mice, Serous Membrane, 0302 clinical medicine, Immunology and Allergy, MESH: Animals, Mast Cells, Cells, Cultured, Mice, Knockout, MESH: Immunoglobulin G, 0303 health sciences, education.field_of_study, biology, Inositol Polyphosphate 5-Phosphatases, MESH: Immunoglobulin E, Degranulation, MESH: Peritoneum, Cell Differentiation, MESH: Mast Cells, Mast cell, Cell biology, medicine.anatomical_structure, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases, MESH : Serous Membrane, MESH: Phosphoric Monoester Hydrolases, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Mast Cells, Peritoneum, MESH : Cell Differentiation, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH : Immunoglobulin G, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Population, Down-Regulation, MESH: Serous Membrane, MESH : Mice, Inbred C57BL, MESH: Models, Immunological, MESH : Immunoglobulin E, 03 medical and health sciences, Immune system, MESH: Mice, Inbred C57BL, MESH : Cells, Cultured, MESH : Mice, medicine, Animals, education, MESH: Mice, MESH : Peritoneum, 030304 developmental biology, MESH: Cell Count, Models, Immunological, Phosphoric Monoester Hydrolases, Mice, Inbred C57BL, Immunoglobulin G, biology.protein, MESH : Mice, Knockout, MESH : Animals, 030215 immunology
Abstract

Bone marrow-derived mast cells (BMMC) have been used extensively as a mast cell model. BMMC, however, are immature cells that have no known physiological equivalent in tissues. They do not respond to IgG immune complexes. They may therefore not be appropriate for studying the physiopathology of IgE-induced allergies or IgG-induced tissue-specific inflammatory diseases which both depend on mature mast cells. Resident peritoneal mast cells are a minor population of differentiated cells that are not readily purified. They, however, can be expanded in culture to generate large numbers of homogeneous cells. We show here that these peritoneal cell-derived mast cells (PCMC) are mature serosal-type mouse mast cells which retain most morphological, phenotypic, and functional features of peritoneal mast cells. Like peritoneal mast cells, PCMC respond to IgG Abs. IgG immune complex-induced responses depended on FcγRIIIA and were negatively regulated by FcγRIIB. We found that a moderate FcγRIIB-dependent negative regulation, due not to a higher FcγRIIIA/FcγRIIB ratio, but to a relatively inefficient use of the lipid phosphatase SHIP1, determines this property of PCMC. PCMC also respond to IgE Abs. IgE-induced PCMC responses, however, differed quantitatively and qualitatively from BMMC responses. PCMC secreted no or much lower amounts of lipid mediators, chemokines, and cytokines, but they contained and released much higher amounts of preformed granular mediators. PCMC, but not BMMC, also contained and, upon degranulation, released molecules with a potent proteolytic activity. These properties make PCMC a useful new model for understanding the physiopathology of mast cells in IgE- and IgG-dependent tissue inflammation.

Published
2007

10. Mouse and human neutrophils induce anaphylaxis

Author

Hajime Karasuyama, Nico van Rooijen, David A. Mancardi, Marc Daëron, Takao Shimizu, Yoshihiro Kita, Bruno Iannascoli, Pierre Bruhns, Friederike Jönsson, Allergologie Moléculaire et Cellulaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), The University of Tokyo (UTokyo), Department of Immune Regulation [Tokyo, Japan], Graduate School of Medical and Dental Sciences [Tokyo, Japan]-Tokyo Medical and Dental University [Japan] (TMDU), Department of Molecular Cell Biology [Amsterdam UMC], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU)-Vrije Universiteit Amsterdam [Amsterdam] (VU), This work was supported by the Institut Pasteur, the Institut National de la Santé et de la Recherche Médicale (INSERM), the Agence Nationale de la Recherche (ANR) (grants 05-JCJC-0236-01 and GENOPAT-09-GENO-014-01), the Fondation pour la Recherche Médicale (FRM) (Programme Allergie 2007), by funding under the Sixth Research Framework Programme of the European Union, Project MUGEN (MUGEN LSHG-CT-2005-005203), by the Société Française d’Allergologie (SFA) (Soutien de la recherche en allergologie 2010) and the Balsan company. F. Jönsson was financially supported by ANR, MUGEN, and is currently a recipient of a fellowship from the FRM. D.A. Mancardi was financially supported by FRM and is currently a recipient of a fellowship from the Institut Pasteur (Bourse Roux). T. Shimizu and Y. Kita are supported in part by Grants-in-Aid from the Ministry of Education, Science, Culture, Sports and Technology of Japan., ANR-05-JCJC-0236,FcR & Allergy,Roles and interactions of human FcR in allergic symptoms induced by human immunoglobulins and allergens: construction of a ' humanized ' mouse model.(2005), ANR-09-GENO-0014,InflammAbs,Contrôle de l'inflammation par les RFc humains dans des modèles murins d'allergie et d'autoimmunité.(2009), European Project: 39516,MUGEN, Martin, Marie, Jeunes chercheuses et jeunes chercheurs - Roles and interactions of human FcR in allergic symptoms induced by human immunoglobulins and allergens: construction of a ' humanized ' mouse model. - - FcR & Allergy2005 - ANR-05-JCJC-0236 - JCJC - VALID, Physiopathologie moléculaire: des maladies rares aux maladies communes - Contrôle de l'inflammation par les RFc humains dans des modèles murins d'allergie et d'autoimmunité. - - InflammAbs2009 - ANR-09-GENO-0014 - GENO - VALID, INTEGRATED FUNCTIONAL GENOMICS IN MUTANT MOUSE MODELS AS TOOLS TO INVESTIGATE THE COMPLEXITY OF HUMAN IMMUNOLOGICAL DISEASE - MUGEN - 39516 - OLD, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Molecular cell biology and Immunology, and CCA - Immuno-pathogenesis

Subjects
Male, MESH: Mice, Inbred NOD, Neutrophils, MESH: Neutrophils, Immunoglobulin E, MESH: Mice, Knockout, Immunoglobulin G, Neutrophil Activation, MESH: Basophils, chemistry.chemical_compound, Mice, 0302 clinical medicine, Mice, Inbred NOD, Medicine, MESH: Animals, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Receptor, Mice, Knockout, MESH: Immunoglobulin G, 0303 health sciences, biology, MESH: Neutrophil Activation, General Medicine, 3. Good health, Basophils, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, Histamine, Anaphylaxis, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Research Article, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Transgenic, Mice, Transgenic, MESH: Receptors, IgG, 03 medical and health sciences, Species Specificity, MESH: Mice, Inbred C57BL, Animals, Humans, MESH: Species Specificity, Platelet Activating Factor, MESH: Mice, 030304 developmental biology, MESH: Platelet Activating Factor, MESH: Humans, Platelet-activating factor, business.industry, Receptors, IgG, medicine.disease, MESH: Male, Mice, Inbred C57BL, MESH: Anaphylaxis, chemistry, Immunology, biology.protein, IgG deficiency, business, 030215 immunology
Abstract

International audience; Anaphylaxis is a life-threatening hyperacute immediate hypersensitivity reaction. Classically, it depends on IgE, FcεRI, mast cells, and histamine. However, anaphylaxis can also be induced by IgG antibodies, and an IgG1-induced passive type of systemic anaphylaxis has been reported to depend on basophils. In addition, it was found that neither mast cells nor basophils were required in mouse models of active systemic anaphylaxis. Therefore, we investigated what antibodies, receptors, and cells are involved in active systemic anaphylaxis in mice. We found that IgG antibodies, FcγRIIIA and FcγRIV, platelet-activating factor, neutrophils, and, to a lesser extent, basophils were involved. Neutrophil activation could be monitored in vivo during anaphylaxis. Neutrophil depletion inhibited active, and also passive, systemic anaphylaxis. Importantly, mouse and human neutrophils each restored anaphylaxis in anaphylaxis-resistant mice, demonstrating that neutrophils are sufficient to induce anaphylaxis in mice and suggesting that neutrophils can contribute to anaphylaxis in humans. Our results therefore reveal an unexpected role for IgG, IgG receptors, and neutrophils in anaphylaxis in mice. These molecules and cells could be potential new targets for the development of anaphylaxis therapeutics if the same mechanism is responsible for anaphylaxis in humans.

Published
2011

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