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Introduction In accordance with its mandate to provide normative guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations [...]

Prolymphocytic leukaemias of B and T cell subtype are rare diseases. Despite recent advances in immunophenotyping and molecular cytogenetics, leading to a better understanding of the underlying cell biology of the prolymphocytic leukaemias, prognosis for these patients remains poor. Purine analogues and monoclonal antibodies have shown efficacy in B-cell prolymphocytic leukaemia although further studies are warranted. Monoclonal antibody therapy with alemtuzumab has significantly improved outcome in T-cell prolymphocytic leukaemia (T-PLL) but responses are still transient and further disease progression is inevitable. While allogeneic stem cell transplant is an attractive option, due to the older age group of T-PLL patients the morbidity and mortality associated with the procedure is significant. [ABSTRACT FROM AUTHOR]

To evaluate the clinical significance of CD21S expression of diffuse large B-cell lymphoma (DLBCL) tumour cells, we compared their clinical features, immunophenotype, response to therapy and outcome in relation to CD21S expression. Between 1987 and 1999, frozen sections from 240 DLBCL cases were examined for CD21S expression by immunohistochemical methods. CD21S expression was detected on the tumour cells of 87 (36%) cases. The median age of the CD21S+ DLBCL cases was 65 years (range: 17–84 years), the male–female ratio was 42:45, and they showed the following clinical features: Eastern Cooperative Oncology Group score >1 in 14%, lactate dehydrogenase greater than normal levels in 38%, extranodal sites >1 in 14%, stages III/IV disease at diagnosis in 29%, B symptoms in 17%, and a high/high–intermediate International Prognostic Index (IPI) in 23%. They also showed a better overall survival ( P = 0·00001, log-rank test) and a better complete remission rate ( P = 0·00004, chi-square test) than CD21S− DLBCL. Moreover, CD21S+ DLBCL showed a better survival than CD21S− DLBCL for both low/low–intermediate and high/high–intermediate risk categories of IPI ( P = 0·045 and P = 0·0016 respectively). Multivariate analysis identified CD21S expression as an independent factor for survival when compared with the five IPI factors. These findings indicate that CD21S expression of DLBCL tumour cells is a useful prognostic factor for survival. [ABSTRACT FROM AUTHOR]

Disease progression in B-cell chronic lymphocytic leukaemia (B-CLL) is determined by the interplay between proliferation kinetics in the proliferating compartment and cell death in the accumulating compartment. Improving our knowledge of cell cycle regulation in B-CLL cells might therefore be important for identifying therapeutic targets. Cyclin E was detected by Western blotting in purified B-CLL cells from peripheral blood samples of all 12 patient tested but not in normal peripheral blood B cells. While cyclin-dependent kinase 2 (cdk2) expression was similar in different samples, p27 and cyclin E expression was highly variable. We further investigated the regulation of p27, cyclin E and cdk2 in an in vitro model of cycling B-CLL cells. Cyclin E and cdk2 expression was increased in B-CLL cells stimulated with a CpG-oligodeoxynucleotide and interleukin-2, while p27 expression rapidly declined. This was accompanied by the increased formation of cyclin E–cdk2 complexes, which were able to phosphorylate Histone H1 in vitro. Pharmacological inhibition of cdk2 activity with Roscovitine-inhibited thymidine incorporation and Histone H1 phosphorylation. We conclude that further evaluation of cyclin E and p27 in peripheral blood cells might help to identify prognostic subgroups. In addition, inhibition of Cyclin E–cdk2 activity by Roscovitine might be a new therapeutic strategy in B-CLL. [ABSTRACT FROM AUTHOR]

The Ikaros transcription factor has been shown to play an important role in the differentiation of both myeloid and lymphoid lineages. Mice heterozygous for a dominant negative (DN) ikaros isoform develop T-cell leukaemia and lymphoma with 100% penetrance. Overexpression of DN Ikaros isoforms has been reported in some forms of leukaemia, such as childhood acute myelomonocytic and monocytic leukaemias, adult B-cell acute lymphoblastic leukaemias (B ALL) and in childhood and adult pre-B ALL. In this study, the expression of Ikaros isoforms in 49 infant and childhood leukaemia patients was analysed by reverse transcription polymerase chain reaction and Western blot analysis. We found overexpression of the DN Ikaros  6 (Ik6) isoform in a subset of leukaemia patients harbouring t(4;11) translocations. To further study the consequences of Ik6 overexpression in B ALL, we inducibly expressed Ik6 in BaF3 cells and found that Ik6 overexpression delayed cell death after interleukin-3 withdrawal, suggesting that overexpression of Ik6 found in t(4;11) B cells could contribute to leukaemogenesis by preventing the apoptosis of cells in an environment with reduced survival factors. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were examined in 84 adult Japanese patients with chronic immune thrombocytopenic purpura (ITP) and 56 race-matched healthy controls. The SNPs examined were within the genes encoding tumour necrosis factor (TNF)- α (−238 G/A and −308 G/A), TNF- β (+252 G/A), and interleukin (IL)-1 β (−511 C/T and +3953 T/C). Of these SNPs, the frequency of the TNF- β (+252) G/G phenotype was significantly higher in ITP patients than in healthy controls (21% vs. 7%, P = 0·04, odds ratio = 3·6, 95% confidence interval 1·1–11·1), while no significant association was detected for the other SNPs. The distribution of the TNF- β (+252) phenotype was not associated with human leucocyte antigen class II alleles or the therapeutic response in ITP patients. The frequency of circulating anti-glycoprotein IIb/IIIa antibody-producing B cells was significantly higher in ITP patients with the TNF- β (+252) G/G phenotype than in those with the G/A or A/A phenotype (11·9 ± 4·9 vs. 6·8 ± 4·9 and 3·7 ± 2·8 per 105 peripheral blood mononuclear cells; P = 0·02 and P < 0·001, respectively). These findings suggest that the SNP located at TNF- β (+252) contributes to susceptibility to chronic ITP by controlling the autoreactive B-cell responses to platelet membrane glycoproteins. [ABSTRACT FROM AUTHOR]

The treatment results of indolent lymphoid malignancies in Chinese are poorly reported. The efficacy of FND (fludarabine 25 mg/m2/d, ×3; mitoxantrone 10 mg/m2/d, ×1; dexamethasone 20 mg/d, ×5; monthly cycles, ×6) in 95 Chinese patients with indolent B-cell malignancies (at diagnosis: 55, relapse/refractory disease: 40) and nine Chinese patients with T-cell large granular lymphocyte leukaemia (T-LGL leukaemia) (at diagnosis: two, refractory disease: seven) was evaluated. For B-cell malignancies, the complete response (CR), partial response (PR) and overall response (OR) rates were 50·5%, 18% and 68·5% respectively. Better results were obtained for primary versus relapse/refractory disease (CR: 60% vs. 37·5%, P = 0·03; OR: 84% vs. 47·5%, P < 0·001; median progression-free survival (PFS): 44 months vs. 22 months; 2-year PFS: 66% vs. 47%, P = 0·039; overall survival (OS): not reached vs. 32%; 2-year OS: 92% vs. 58%, P < 0·001). Responsive patients (CR/PR) had a better median PFS (44 months vs. 5 months, P < 0·001) and OS (67 months vs. 13 months, P < 0·001) than unresponsive patients. For T-LGL leukaemia, the CR and molecular-remission rates were 56% and 67% (median follow-up: 23 months). FND is an active regimen for the treatment of indolent B- and T-cell malignancies in Chinese patients, with results comparable with Western patients with similar indolent lymphomas. [ABSTRACT FROM AUTHOR]

Multiple mechanisms exist by which tumour cells can escape CD95-mediated apoptosis. Previous studies by our laboratory have shown that primary B cells from non-Hodgkin's Lymphoma (B-NHL) were resistant to CD95-induced cell death. In the current study, we have analysed the mechanisms underlying CD95 resistance in primary human lymphoma B cells. We report that FADD (FAS-associated death domain protein) and caspase-8 were constitutively expressed in lymphoma B cells and that the CD95 pathway was blocked upstream to caspase-8 activation. However, caspase-8 was processed and functional after treatment with staurosporine (STS). We found that the expression levels of FLICE (FADD-like interleukin-1 beta-converting enzyme)-Inhibitory Protein (c-FLIP) and Bcl-2-related proteins were heterogeneous in B-NHL cells and were not related to CD95 resistance. Finally, we report the absence of a CD95-induced signalling complex [death-inducing signalling complex (DISC)] in lymphoma B cells, with no FADD and caspase-8 recruitment to CD95 receptor. In contrast, DISC formation was observed in CD95-resistant non-tumoural (NT) B cells. Therefore, we propose that the absence of DISC formation in primary lymphoma B cells may contribute to protect these cells from CD95-induced apoptosis. [ABSTRACT FROM AUTHOR]

In patients with neoplastic meningitis (NM), the rapid institution of intrathecal therapy may ameliorate the course of disease, indicating that a timely diagnosis is clinically relevant. As immunocytology (IC) of cerebrospinal fluid and magnetic resonance imaging (MRI), as diagnostic methods, have potential pitfalls, the present study assessed the results of both methods, to determine the predictive capability of the initial evaluations with respect to the risk that the patient would develop NM during the course of their disease. A total of 166 individuals with B-cell non-Hodgkin's lymphoma (B-NHL; n = 95), B-acute lymphocytic leukaemia (ALL; n = 18), acute myeloid leukaemia ( n = 27) or solid tumours ( n = 26), with at least one definitive IC and MRI result within 3 weeks, were evaluated at a median follow-up of 29·5 months (range 6–53 months). IC and MRI results reached the highest concordance (98%) in B-NHL patients and were most discordant in ALL patients (43%). In haematological malignancies, IC displayed considerable sensitivity, ranging from 89% to 95%, while MRI had very low sensitivity. Conversely, MRI showed high sensitivity (100%) and specificity (92%) in solid tumours. We conclude that IC is of particular value in the diagnosis of NM due to haematological malignancies while MRI is superior to IC in the diagnosis of NM due to solid tumours. [ABSTRACT FROM AUTHOR]

Novel N-glycosylation sites are introduced by somatic mutation into the V genes of the majority of follicular lymphomas. Sites are positively selected and rare in normal memory B cells, indicating a potential role in tumour survival in the germinal centre (GC). The incidence of c. 40% in diffuse large B-cell lymphomas (DLBCL) parallels the known heterogenity of the disease. Immunodeficiency-related non-Hodgkin's lymphomas (NHL) include post-transplant lymphoproliferative disorders (PTLD) and acquired immunodeficiency syndrome-related NHL (AIDS-NHL). Most PTLD derive from B cells that carry mutated VH genes and that have completed the GC reaction. All AIDS-NHL carry mutated VH genes and variable features of GC or post-GC cells. To determine if N-glycosylation is a feature of immunodeficiency-related lymphomas, we analysed the VH genes of 19 PTLD and 36 AIDS-NHL. Novel sites were rare in PTLD (4/19), similar to memory B cells ( P = 0·15). AIDS-NHL, including DLBCL and Burkitt's lymphomas (BL), showed heterogeneity with 16 of 36 (44%) having novel sites. The findings indicate no selection of N-glycosylation sites in PTLD, consistent with post-GC features. The variable incidence of N-glycosylation sites in AIDS-NHL mirrors that in DLBCL and sporadic BL of immunocompetent hosts, supporting the known heterogeneity of these disorders, and possibly pointing to distinct routes of tumour development. [ABSTRACT FROM AUTHOR]

Dysregulation of fibroblast growth factor receptor 3 ( FGFR3) by the translocation t(4;14)(p16;q32) occurs in 15% of multiple myeloma (MM) patients and confers a growth and survival advantage to malignant plasma cells. As FGFR3 is a molecular target, we assessed the therapeutic potential of the FGFR-specific tyrosine kinase inhibitors SU5402 and SU10991 in MM. SU5402 inhibited FGFR3 phosphorylation in vitro and in murine MM tumour models. B cells dependent on FGFR3 for survival were specifically sensitive to SU5402. A panel of 11 human myeloma cell lines was studied, five bearing the t(4;14) translocation. The KMS11 human myeloma cell line, which expresses constitutively active mutant FGFR3, displayed an 85% decrease in S-phase cells, a 95% increase in G0/G1 cells, and 4·5-fold increase in apoptotic cells after 72 h treatment with 10 μmol/l SU5402. Activated extracellular signal-regulated kinases  1 and 2 and signal transducer and activator of transcription 3 were rapidly down-regulated after SU5402 treatment. In human myeloma cell lines expressing wild-type FGFR3 the stimulating effect of aFGF ligand was abrogated by SU5402 treatment. Myeloma cells lacking the t(4;14) or with the t(4;14) and a secondary RAS mutation did not respond to therapy. These findings support the development of clinical trials of early intervention with FGFR3 inhibitors in t(4;14) myeloma. [ABSTRACT FROM AUTHOR]

We have investigated whether intracellular signal transduction molecules can be used as immunohistological markers of normal and neoplastic human leucocytes in routine tissue sections. We obtained selective labelling of white cells for eight such molecules (the ‘linker’ molecules SLP-76 and BLNK, the Src family kinases Lyn, Fyn, Syk and Hck, and the phospholipases PLC- γ1 and PLC- γ2). Antibodies to SLP-76 and PLC- γ1 selectively labelled T cells, and antibodies to BLNK, Lyn, Fyn, Syk and PLC- γ2 labelled B cells (although Fyn immunostaining was restricted to mantle zone B cells). Antibodies to the Syk and Hck kinases labelled probable thymocyte precursors at the periphery of the thymic cortex. In addition to lymphoid cells, several other leucocyte types were immunostained (e.g. SLP-76, Lyn, Syk and Hck were found in megakaryocytes, myeloid cells and/or macrophages, and PLC- γ2 was detected in arterial endothelium). SLP-76 and PLC- γ1 were found in most T-cell lymphomas studied, and some B-cell lymphomas were also positive for PLC- γ1 (e.g. diffuse large cell and Burkitt's lymphoma). The five B cell-associated markers were found in most B-cell non-Hodgkin's lymphomas, although some diffuse large B-cell lymphomas were negative (e.g. for Lyn) and anti-Fyn tended not to stain small B-cell neoplasms. The observation that a range of leucocyte signalling molecules can be detected in routine biopsies offers new possibilities for studying normal and neoplastic human white cells in diagnostic tissue samples. [ABSTRACT FROM AUTHOR]

Primary intraocular lymphoma (PIOL) is a rare presentation of lymphoma that is particularly difficult to recognize. In our institution, 36 cases of PIOL were diagnosed between March 1997 and July 2002. The recognition of lymphoma cells by cytology with or without immunophenotyping on slides generated a strong suspicion of the diagnosis in 34 of 36 cases. The diagnosis was confirmed by measurement of interleukin-10 (IL-10) in the vitreous humour or aqueous humour; high levels were observed in 35 of 36 cases, all were of B-cell origin. As expected, the only case with T-cell lymphoma had a very low level of IL-10. Furthermore, IL-10 levels excluded this diagnosis in two cases that were incorrectly suspected of PIOL after cytological examination. Finally, detection of clonality by polymerase chain reaction techniques, performed in 29 cases, represented a helpful tool in diagnosing PIOL as this approach definitively confirmed the diagnosis of B- or T-cell lymphoma in 17 cases. [ABSTRACT FROM AUTHOR]

B-cell chronic lymphocytic leukaemia (B-CLL) is a neoplastic disorder characterized by defective apoptosis, cell accumulation in G0/G1, and high expression of BCL2 oncogene. Intracellular cyclic adenosine monophosphate (cAMP) accumulation increases the chemosensitivity of B-CLL cells in vitro and in vivo. In the present study, we investigated the effects of β2-adrenergic compounds, well known cAMP-inducing drugs, on the in vitro survival of leukaemia cells. In contrast to the short-acting β2-mimetic (β2Mim) salbutamol, a consistent pro-apoptotic effect was observed with the long-acting β2Mim salmeterol and formoterol. Normal B cells isolated from control donors were totally resistant to the above molecules. These compounds also increased chlorambucil- and fludarabine-induced death of B-CLL cells. Blockade of β-adrenergic receptor signalling or cAMP did not alter B-CLL apoptosis with β2 Mimagents. Leukaemia cell apoptosis by β2Mim correlated with an increase in calcium influx, decreased bcl-2 protein and mRNA levels, increase in BAX gene expression and a marked rise in BCL2/BAX mRNA ratios. Interleukin-4, a cytokine that increases bcl-2 expression in B-CLL cells, rescued leukaemia cell from apoptosis with β2Mim. These data show that long-acting β2-adrenergic agents promote apoptotic leukaemia cell death through an adrenoreceptor- and cAMP-independent, Ca2+-dependent mechanism. [ABSTRACT FROM AUTHOR]

Despite a successful outcome of the anti-D prophylaxis programme, alloimmunization still occurs. The aim of this study was to estimate the frequency of Rh-specific B lymphocytes in the peripheral blood of nine Rh-alloimmunized individuals at different time intervals after parturition. The donors’ B lymphocytes were transformed with Epstein–Barr virus (EBV) and cultured at different cell densities over a feeder of human fetal fibroblasts. Culture supernatants were screened for human immunoglobulin by enzyme-linked immunosorbent assay (ELISA) and for anti-Rh antibody by using a direct haemagglutination technique. The percentage of CD19+ B lymphocytes in peripheral blood was determined by flow cytometry, and the frequency of Rh-specific B lymphocytes was estimated by limiting-dilution assay (LDA). The frequency of Rh-specific B lymphocytes varied from 1 : 150 to 1 : 27 850 in different donors. There was a decrease in this frequency and level of anti-Rh antibody with increase in time interval between bleeding and last exposure to the antigen. Furthermore, a positive correlation was observed between the titre of Rh-specific antibody and frequency of Rh-specific B cells in each of three subjects bled at multiple time-points postdelivery. The magnitude of the specific antibody response to Rh antigens varies greatly in Rh-alloimmunized women, which partly reflects the difference in frequency of specific B cells in these individuals. [ABSTRACT FROM AUTHOR]

Background.Studies indicate that following septic insult there is development of generalized immune dysfunction in T cells, B cells and phagocytes, which is thought to contribute to morbidity and mortality. Specifically, there is a shift in the lymphocytes of septic animals toward an increased release of Th2 cytokines. NK-T cells have been shown to contribute to propagation of the Th2 response. The influence of NK-T cells on the immune response to septic challenge is poorly understood. In this study, we examine whether NK-T cells contribute to the immune dysfunction seen following the onset of polymicrobial sepsis, as produced by cecal ligation and puncture (CLP).Materials and methods.Male 129S1/SvImJ mice were pretreated with either rat IgG (isotypic control) or monoclonal antibody to CD1d (clone 1B1) (0.5 mg), which blocks signaling/antigen presentation via the CD1d cell surface receptor, thereby, ablating the activation and differentiation of the NK-T cells. Septic survival with and without anti-CD1d (CLP/CD1d) pretreatment was assessed. Mice sacrificed 24 h after CLP were assessed for change in splenic %NK-T cell (via flourescense activated cell sector) and for splenic, hepatic, and lymphoid/macrophage production of pro-inflammatory or anti-inflammatory cytokines (via enzyme-linked immunosorbent assay).Results.Administration of anti-CD1d reduced septic mortality 35% at 6–10 d (n = 23 mice/group) (P < .05). There was a consistent increase in the %CD3+ NK1.1+ cell population (NK-T cells) in septic mice (1.706%), which was markedly suppressed by pretreatment with anti-CD1d (0.592%). IL-6 and IL-10 levels were suppressed by anti-CD1d in the spleen and blood.Conclusions.Together these findings imply not only that NK-T cells may play a role in mediating the immune suppression seen in bacterial sepsis, but that inhibition of their activation promotes survival to septic challenge. [Copyright &y& Elsevier]

Summary. The available data on rituximab in combination with chemotherapy confirm that the addition of an independently active biological agent to full-dose standard chemotherapy results in higher rates of complete response, lower rates of relapse, prolonged survival, little additional toxicity and no compromise of the dose intensity of standard chemotherapy regardless of age and risk group. Given the strength of these data, the British Committee for Standards in Haematology believes that rituximab should be available for prescription by UK haematologists and oncologists according to its licensed indication in patients with diffuse large B-cell lymphoma until further data are available to confirm or refute these results. We consider that the use of rituximab with chemotherapy in aggressive lymphoma is cost-effective and that failure to support its introduction will be strongly in conflict with professional and patient opinion. [ABSTRACT FROM AUTHOR]

This document is a correction notice for a paper on the potential bioactive compound bromelain. The authors have identified errors in one section of the paper and provide revised references. The corrected table includes therapeutic studies of bromelain based on experimental studies. The document also includes a compilation of various scientific studies and articles related to the use of bromelain for various medical purposes. The studies explore the potential benefits of bromelain in treating conditions such as cancer, inflammation, thrombosis, and pain. The document provides a comprehensive overview of the scientific research on bromelain and its potential applications in medicine. [Extracted from the article]

The 80+ existing autoimmune disorders (ADs) affect billions with little prevention or treatment options, except for temporary symptomatic management, leading to enormous human suffering and a monumental financial burden. The autoantibodies formed in most ADs have been identified, allowing the development of novel anti-idiotypic antibodies to mute the autoantibodies using vaccines. Nucleoside vaccines have been successfully tested as antigen-specific immunotherapies (ASI), with mRNA technology offering multi-epitope targeting to mute multiple autoantibodies. This paper proposes using mRNA technology to produce anti-idiotypic antibodies with broad effectiveness in preventing and treating them. This paper delves into the state-of-the-art mRNA design strategies used to develop novel ASIs by selecting appropriate T cell and B cell epitopes to generate anti-idiotypic antibodies. The low cost and fast development of mRNA vaccines make this technology the most affordable for the global control of ADs. [ABSTRACT FROM AUTHOR]

Over the past century, the field of antibody discovery has undergone significant evolution, excluding the current exploration stage of artificial intelligence‐based antibody generation and the often overlooked non‐animal sourced antibody discovery, which typically requires mature in vitro affinity and the selection of high‐quality antigen formulations. This journey has traversed various stages, from methods involving serum‐based antibody acquisition, the isolation of B cells capable of perpetual antibody production through hybridoma technology, to the in‐depth exploration of genetic material using the phage display system, and the current stage involving diverse single B cell screening techniques. Additionally, the emergence of machine learning has brought impressive scientific and technological breakthroughs across research domains, proving to be a powerful application in the field of antibody discovery. However, each technique comes with its limitations, such as variability and control challenges in serum‐based acquisition, lengthy and difficult hybridoma‐derived antibody development, potential limitations in sequence and epitope diversity due to immunization biases in phage display techniques, and costly single B cell screening. Protein mass spectrometry sequencing, with shorter acquisition time and lower costs, is seen as a shortcut by diagnostic companies, impacting traditional antibody development. In diagnostic antibody development, methodological differences in downstream assays and the impact of constant regions outside the Fv core are often neglected. This paper deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products. [ABSTRACT FROM AUTHOR]

Simple Summary: The B cell receptor (BCR) is a membrane-bound protein complex that is required for the normal development of B cells. BCR signalling is also involved in the pathogenesis of B cell cancers. While there is substantial literature on genomic analyses of the BCR, there are limited proteomic studies of receptor structure and its interactions with neighbouring proteins. This is partly due to the location of the BCR in the surface-membrane lipid environment that has limited the ability to enrich the complex for proteomic analysis. Here, we report an enrichment technique that can be used for mass spectrometry analyses of the BCR from live B cells. B cells are central to the adaptive immune response and provide long-lasting immunity after infection. B cell activation is mediated by the surface membrane-bound B cell receptor (BCR) following recognition of a specific antigen. The BCR has been challenging to analyse using mass spectrometry (MS) due to the difficulty of isolating and enriching this membrane-bound protein complex. There are approximately 120,000 BCRs on the B cell surface; however, depending on the B cell activation state, there may be hundreds-of-millions to billions of proteins in a B cell. Consequently, advanced proteomic techniques such as MS workflows that use purified proteins to yield structural and protein-interaction information have not been published for the BCR complex. This paper describes a method for enriching the BCR complex that is MS-compatible. The method involves a Protein G pull down on agarose beads using an intermediary antibody to each of the BCR complex subcomponents (CD79a, CD79b, and membrane immunoglobulin). The enrichment process is shown to pull down the entire BCR complex and has the advantage of being readily compatible with further proteomic study including MS analysis. Using intermediary antibodies has the potential to enrich all isotypes of the BCR, unlike previous methods described in the literature that use protein G-coated beads to directly pull down the membrane IgG (mIgG) but cannot be used for other mIg isotypes. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune condition frequently found in rheumatological patients that sometimes raises diagnosis and management problems. The pathogenesis of the disease is complex and involves the activation of many cells and intracellular signaling pathways, ultimately leading to the activation of the innate and acquired immune system and producing extensive tissue damage. Along with joint involvement, RA can have numerous extra-articular manifestations (EAMs), among which lung damage, especially interstitial lung disease (ILD), negatively influences the evolution and survival of these patients. Although there are more and more RA-ILD cases, the pathogenesis is incompletely understood. In terms of genetic predisposition, external environmental factors act and subsequently determine the activation of immune system cells such as macrophages, neutrophils, B and T lymphocytes, fibroblasts, and dendritic cells. These, in turn, show the ability to secrete molecules with a proinflammatory role (cytokines, chemokines, growth factors) that will produce important visceral injuries, including pulmonary changes. Currently, there is new evidence that supports the initiation of the systemic immune response at the level of pulmonary mucosa where the citrullination process occurs, whereby the autoantibodies subsequently migrate from the lung to the synovial membrane. The aim of this paper is to provide current data regarding the pathogenesis of RA-associated ILD, starting from environmental triggers and reaching the cellular, humoral, and molecular changes involved in the onset of the disease. [ABSTRACT FROM AUTHOR]

The Bursa of Fabricius, an avian unique humoral immune organ, is instrumental to B cell development. Bursal-derived peptide BP9 fosters B-cell development and formation. Yet, the exact mechanism wherein BP9 impacts B cell differentiation and antigenic presentation remains undefined. In this paper, B cell activation and differentiation in the spleen cells from mice immunized with the AIV vaccine and BP9 were detected following flow cytometry (FCM) analysis. Furthermore, the molecular mechanism of BP9 in B cell differentiation in vivo was investigated with RNA sequencing technology. To verify the potential functional mechanism of BP9 in the antigenic presentation process, the transcriptome molecular basis of chicken macrophages stimulated by BP9 was measured via high-throughput sequencing technology. The results proved that when given in experimental dosages, BP9 notably accelerated total B cells, and enhanced B-cell differentiation and plasma cell production. The gene expression profiles of B cells from mice immunized with 0.01 mg/mL BP9 and AIV vaccine disclosed that 0.01 mg/mL BP9 initiated the enrichment of several biological functions and significantly stimulated key B-cell pathways in immunized mice. Crucially, a total of 4093 differentially expressed genes were identified in B cells with BP9 stimulation, including 943 upregulated genes and 3150 downregulated genes. Additionally, BP9 induced various cytokine productions in the chicken macrophage HD11 cells and activated 9 upregulated and 20 downregulated differential miRNAs, which were involved in various signal and biological processes. Furthermore, BP9 stimulated the activation of multiple transcription factors in HD11 cells, which was related to antigen presentation processes. In summary, these results suggested that BP9 might promote B cell differentiation and induce antigen presentation, which might provide the valuable insights into the mechanism of B cell differentiation upon bursal-derived immunomodulating peptide stimulation and provide a solid experimental groundwork for enhancing vaccine-induced immunity. [ABSTRACT FROM AUTHOR]

Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca2+ signaling, interference with cellular signaling pathways, and epigenetic modifications. By detailing the absorption, distribution, metabolism, and excretion (ADME) of Cd, alongside its interactions with cellular components such as mitochondria and DNA, this paper highlights the extensive damage caused by Cd2+ at the cellular and tissue levels. The role of Cd in inducing oxidative stress—a pivotal mechanism behind its toxicity—is discussed with emphasis on how it disrupts the balance between oxidants and antioxidants, leading to cellular damage and apoptosis. Additionally, the review covers Cd's impact on signaling pathways like Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor Protein 53 (p53) pathways, illustrating how its interference with these pathways contributes to pathological conditions and carcinogenesis. The epigenetic effects of Cd, including DNA methylation and histone modifications, are also explored to explain its long-term impact on gene expression and disease manifestation. This comprehensive analysis not only elucidates the mechanisms of Cd toxicity but also underscores the critical need for enhanced strategies to mitigate its public health implications. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this data paper is to describe a collection of 33 genomic, transcriptomic and epigenomic sequencing datasets of the B-cell acute lymphoblastic leukemia (ALL) cell line REH. REH is one of the most frequently used cell lines for functional studies of pediatric ALL, and these data provide a multi-faceted characterization of its molecular features. The datasets described herein, generated with short- and long-read sequencing technologies, can both provide insights into the complex aberrant karyotype of REH, and be used as reference datasets for sequencing data quality assessment or for methods development. Data description: This paper describes 33 datasets corresponding to 867 gigabases of raw sequencing data generated from the REH cell line. These datasets include five different approaches for whole genome sequencing (WGS) on four sequencing platforms, two RNA sequencing (RNA-seq) techniques on two different sequencing platforms, DNA methylation sequencing, and single-cell ATAC-sequencing. [ABSTRACT FROM AUTHOR]

Introduction: B cells play a pivotal role in adaptive immunity which has been extensively characterised primarily via flow cytometry-based gating strategies. This study addresses the discrepancies between flow cytometry-defined B cell subsets and their high-confidence molecular signatures using single-cell multiomics approaches. Methods: By analysing multi-omics single-cell data from healthy individuals and patients across diseases, we characterised the level and nature of cellular contamination within standard flow cytometric-based gating, resolved some of the ambiguities in the literature surrounding unconventional B cell subsets, and demonstrated the variable effects of flow cytometric-based gating cellular heterogeneity across diseases. Results: We showed that flow cytometric-defined B cell populations are heterogenous, and the composition varies significantly between disease states thus affecting the implications of functional studies performed on these populations. Importantly, this paper draws caution on findings about B cell selection and function of flow cytometric-sorted populations, and their roles in disease. As a solution, we developed a simple tool to identify additional markers that can be used to increase the purity of flow-cytometric gated immune cell populations based on multi-omics data (AlliGateR). Here, we demonstrate that additional non-linear CD20, CD21 and CD24 gating can increase the purity of both naïve and memory populations. Discussion: These findings underscore the need to reconsider B cell subset definitions within the literature and propose leveraging single-cell multi-omics data for refined characterisation. We show that single-cell multi-omics technologies represent a powerful tool to bridge the gap between surface marker-based annotations and the intricate molecular characteristics of B cell subsets. [ABSTRACT FROM AUTHOR]

Background: The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells. Results: We found an age-dependent reduction in the proportion of germinal center B cell population (BGC) and its T cell counterpart (T follicular helper germinal center cells, TfhGC). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells within the freshly isolated TMC fraction than those from older ones. We demonstrated the accumulation of a B cell subset (CD20+CD39highCD73+ cells) metabolically adapted to catabolize adenosine triphosphate (ATP) as patients get older. To finish, tonsillar B cells from patients at different ages did not show differences in their proliferative response to stimulation ex vivo, in bulk TMC cultures. Conclusions: This paper sheds light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the excised tonsils over time. They are indicative of a transition from an effector type of immune response, typically oriented to reduce pathogen burden early in life, to the development of an immunosuppressive microenvironment at later stages, when tissue damage control gets critical provided the time passed under immune attack. Noteworthy, when isolated from such histologic microenvironment, older tonsillar B cells seem to level their proliferation capacity with the younger ones. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites. [ABSTRACT FROM AUTHOR]

The article focuses on the best basic science research on multiple sclerosis (MS) in 2012. It states several researchers working on MS, including S. R. Choi and colleagues on the role of meningeal inflammation in MS, R. P. Lisak and colleagues on the contribution of B cells to the grey matter (GM) pathology of MS, and A. Chang and colleagues on the effect of remyelination in MS. It says that the work of Robin Franklin's group on enhanced remyelination in MS is the best research in 2012.

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC. [ABSTRACT FROM AUTHOR]

Helminths are multicellular parasites that are a substantial problem for both human and veterinary medicine. According to estimates, 1.5 billion people suffer from their infection, resulting in decreased life quality and burdens for healthcare systems. On the other hand, these infections may alleviate autoimmune diseases and allergy symptoms. The immune system is programmed to combat infections; nevertheless, its effector mechanisms may result in immunopathologies and exacerbate clinical symptoms. This review summarizes the role of the immune response against worms, with an emphasis on the Th2 response, which is a hallmark of helminth infections. We characterize non-immune cells (enteric tuft cells—ETCs) responsible for detecting parasites, as well as the role of hematopoietic-derived cells (macrophages, basophils, eosinophils, neutrophils, innate lymphoid cells group 2—ILC2s, mast cells, T cells, and B cells) in initiating and sustaining the immune response, as well as the functions they play in granulomas. The aim of this paper is to review the existing knowledge regarding the immune response against helminths, to attempt to decipher the interactions between cells engaged in the response, and to indicate the gaps in the current knowledge. [ABSTRACT FROM AUTHOR]

Human B cell immortalization that maintains the constant growth characteristics and antibody expression of B cells in vitro is very critical for the development of antibody drugs and products for the diagnosis and bio-therapeutics of human diseases. Human B cell immortalization methods include Epstein-Barr virus (EBV) transformation, Simian virus 40 (SV40) virus infection, in vitro genetic modification, and activating CD40, etc. Immortalized human B cells produce monoclonal antibodies (mAbs) very efficiently, and the antibodies produced in this way can overcome the immune rejection caused by heterologous antibodies. It is an effective way to prepare mAbs and an important method for developing therapeutic monoclonal antibodies. Currently, the US FDA has approved more than 100 mAbs against a wide range of illnesses such as cancer, autoimmune diseases, infectious diseases, and neurological disorders. This paper reviews the research progress of human B cell immortalization, its methods, and future directions as it is a powerful tool for the development of monoclonal antibody preparation technology. [ABSTRACT FROM AUTHOR]

The article offers update on bone fracture prevention and treatments for conditions such as osteoporosis. It discusses findings of several research including fracture repair via bone remodeling using osteoclasts, potential of high frequency sound waves to convert bone marrow derived mesenchymal stem cells into bone cells, and a demineralised bone paper biomaterial used to advanced the understanding of bone biology, model disease progression and screen drug responses.

STUDY QUESTION What are the similarities and differences in endometrial B cells in the normal human endometrium and benign reproductive pathologies? SUMMARY ANSWER Endometrial B cells typically constitute <5% of total endometrial CD45+ lymphocytes, and no more than 2% of total cells in the normal endometrium, and while their relative abundance and phenotypes vary in benign gynaecological conditions, current evidence is inconsistent. WHAT IS KNOWN ALREADY B cells are vitally important in the mucosal immune environment and have been extensively characterized in secondary lymphoid organs and tertiary lymphoid structures (TLSs), with the associated microenvironment germinal centre. However, in the endometrium, B cells are largely overlooked, despite the crucial link between autoimmunity and reproductive pathologies and the fact that B cells are present in normal endometrium and benign female reproductive pathologies, scattered or in the form of lymphoid aggregates (LAs). A comprehensive summary of current data investigating B cells will facilitate our understanding of endometrial B cells in the endometrial mucosal immune environment. STUDY DESIGN, SIZE, DURATION This systematic review retrieved relevant studies from four databases (MEDLINE, EMBASE, Web of Science Core Collection and CINAHL) from database inception until November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS The search strategy combined the use of subject headings and relevant text words related to 'endometrium', 'B cells' and B-cell derivatives, such as 'antibody' and 'immunoglobulin'. Non-benign diseases were excluded using cancer-related free-text terms, and searches were limited to the English language and human subjects. Only peer-reviewed research papers were included. Each paper was graded as 'Good', 'Fair' or 'Poor' quality based on the NEWCASTLE-OTTAWA quality assessment scale. Only 'Good' quality papers were included. MAIN RESULTS AND THE ROLE OF CHANCE Twenty-seven studies met the selection criteria and were included in this review: 10 cross-sectional studies investigated B cells in the normal endometrium; and 17 case–control studies compared the characteristics of endometrial B cells in control and benign female reproductive pathologies including endometritis, endometriosis, infertility, abnormal uterine bleeding, endometrial polyps and uterine fibroids. In all studies, B cells were present in the endometrium, scattered or in the form of LAs. CD20+ B cells were more abundant in patients with endometritis, but the data were inconsistent as to whether B-cell numbers were increased in endometriosis and patients with reproductive pathologies. LIMITATIONS, REASONS FOR CAUTION Although only 'good' quality papers were included in this systematic review, there were variations in patients' age, diagnostic criteria for different diseases and sample collection time among included studies. Additionally, a large number of the included studies only used immunohistochemistry as the identification method for endometrial B cells, which may fail to provide an accurate representation of the numbers of endometrial B cells. WIDER IMPLICATIONS OF THE FINDINGS Histological studies found that endometrial B cells are either scattered or surrounded by T cells in LAs: the latter structure seems to be under hormonal control throughout the menstrual cycle and resembles TLSs that have been observed in other tissues. Further characterization of endometrial B cells and LAs could offer insights to endometrial B-cell function, particularly in the context of autoimmune-associated pathologies, such as endometriosis. Additionally, clinicians should be aware of the limited value of diagnosing plasma cell infiltration using only CD138. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Finox Biotech. The authors have no conflicts of interest to declare. PROSPERO REGISTRATION NUMBER This systematic review was registered in PROSPERO in January 2020 (PROSPERO ID: CRD42020152915). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this review is to discuss the significance of IL-17 in SLE and the potential of IL-17-targeted therapy. Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs and tissues throughout the body. It is characterized by overactive B and T cells and loss of immune tolerance to autoantigens. Interleukin-17 (IL-17) is a cytokine that promotes inflammation and has been implicated in the pathogenesis of several autoimmune diseases as well as inflammatory diseases. In in vitro cellular experiments in lupus susceptible mice or SLE patients, there is substantial evidence that IL-17 is a highly promising therapeutic target. Methods: We searched papers from PubMed database using the search terms, such as interleukin-17, systemic lupus erythematosus, treatment targets, T cells, lupus nephritis, and other relevant terms. Results: We discuss in this paper the molecular mechanisms of IL-17 expression, Th17 cell proliferation, and the relationship between IL-17 and Th17. The significance of IL-17 in SLE and the potential of IL-17-targeted therapy are further discussed in detail. Conclusion: IL-17 has a very high potential for the development as a star target in SLE. [ABSTRACT FROM AUTHOR]