RESUMEN

Lymphoblastoid cell lines (LCLs) are immortalised peripheral B lymphocytes, transformed via infection with Epstein Barr virus (EBV). The use of LCLs to study B cell function remains controversial and core markers to define physiological B cell populations are not consistent between studies of physiological B cells and LCLs. A consensus on the nature of these commonly used cell lines has not been reached. Recently, a core set of markers to subtype peripheral B cells was proposed, addressing the lack of agreed markers for B cell characterisation. In this present study, the consensus panel was applied to describe the B cell subtypes in LCLs. We found that LCLs were generally not physiologically representative of B cells, with most cells harbouring marker combinations absent on peripheral B cells. Some B cell subtyping markers were fundamentally altered during EBV transformation to LCLs (e.g. CD19, CD21). Notably, most LCLs secreted IgG but the associated marker combinations were predominantly only present in vitro following EBV transformation. This study therefore informs interpretation of past investigations, and planning of future studies using LCLs, as these cells are unlikely to behave like their pre-transformed B cell subtype.

RESUMEN

In this study, we aimed to investigate the changes in the B cell subpopulations after homologous or heterologous COVID-19 boosters. Blood samples were collected after baseline (3-5 months after two doses of CoronaVac), 1 and 3 months after BNT162b2 (n=28 and n=6), and CoronaVac (n=7 and n=4) boosters. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with B cell markers, the ratios of naïve (CD19+CD20+CD27-), memory (CD19+CD20+CD27+), memory B cells expressing IgG (CD19+CD20+CD27+IgG+), and effector memory B cells (CD19+CD20+CD27+CD38+) were identified with flow cytometry. Significantly higher expression of memory B cells was observed in one month with BNT162b2 (12.16% one month, 5.98% three months) and CoronaVac (14.18% one month, 9.00% three months) boosters. IgG expressing memory B cell expression was significantly higher with BNT162b2 than with CoronaVac booster in one month (22.70% and 13.95%, respectively). The ratio of effector B cells in the first month after CoronaVac booster (25.44%) was significantly higher than the BNT162b2 booster (9.90%, p =0.0263).

RESUMEN

The interest in regulatory B cells (Bregs) began in the 1970s with the evidence that B cells could downregulate the immune system by the production of "inhibitory" antibodies. Subsequently, a series of results from different studies have emphasized that B cells have antibody-independent immunoregulatory functions. Since then, different subsets of B cells with regulatory functions and their development and mechanisms of action have been identified both in human and in animal models of inflammation, transplantation, and autoimmunity. The present review outlines the suggested pathways by which Bregs develop, describes the different subsets of Bregs with their phenotypes and function as well as their role in transplantation, highlighting the differences between human and animal studies throughout.

Asunto(s)

RESUMEN

T follicular helper (Tfh) cells are known to support effector B cells and enhance autoimmunity; however, the association between the Tfh cells and B cells in ankylosing spondylitis (AS) is unclear. The aim of the present study was to measure the frequency of circulating cluster of differentiation (CD)4+ C-X-C chemokine receptor type 5 (CXCR5)+ Tfh cells and B cell subtypes in peripheral blood from patients with AS, and evaluate the correlation of these factors. Percentages of peripheral blood circulating CD4+CXCR5+ Tfh cells and B cell subtypes were measured via flow cytometry and the disease activity of individual patients was measured using the Bath AS Disease Activity Index (BASDAI). The potential association among these measures was analyzed via Spearman's or Pearson's correlations. In comparison with those in healthy controls (HC), significantly increased percentages of CD4+CXCR5+ cTfh, CD4+CXCR5+ programmed death 1+, CD4+CXCR5+ inducible T cell costimulator (ICOS)+, CD3+CD8-CXCR5+ interleukin (IL)-21+ T cells, CD19+CD27high plasmablast and CD19+CD38+ antibody-secreting B cells were detected in patients with AS, whereas there was no significant difference in CD19+CD27- naïve B cells and CD19+CD27+ memory B cells. When Patients with AS were divided into high and low activity groups, significantly higher percentages of CD4+CXCR5+, CD3+CD8-CXCR5+IL-21+ T cells, CD19+CD27- naïve B cells and CD19+CD38+ antibody-secreting B cells, and lower CD19+CD27+ memory B cells were detected in high activity AS group compared with the low activity AS group. In addition, percentages of CD4+CXCR5+ circulating (c)Tfh, CD3+CD8-CXCR5+IL-21+ T and CD19+CD38+ antibody-secreting B cells were positively correlated with BASDAI values. Furthermore, the percentage of CD4+CXCR5+ cTfh cells was positively correlated with CD19+CD38+ antibody-secreting B cells and the percentage of CD3+CD8-CXCR5+IL-21+ T cells was positively correlated with CD19+CD27- naïve B cells in patients with AS. These findings suggest that CD4+CXCR5+ cTfh, CD3+CD8-CXCR5+IL-21+ T and CD19+CD38+ antibody-secreting B cells may participate in the pathogenesis of AS because of their distinct functions. As such, levels of cTfh and B cell subtypes may be a useful biomarker for the evaluation of disease activity in patients with AS.

RESUMEN

DNA methylation levels vary markedly by cell-type makeup of a sample. Understanding these differences and estimating the cell-type makeup of a sample is an important aspect of studying DNA methylation. DNA from leukocytes in whole blood is simple to obtain and pervasive in research. However, leukocytes contain many distinct cell types and subtypes. We propose a two-stage model that estimates the proportions of six main cell types in whole blood (CD4+ T cells, CD8+ T cells, monocytes, B cells, granulocytes, and natural killer cells) as well as subtypes of T and B cells. Unlike previous methods that only estimate overall proportions of CD4+ T cell, CD8+ T cells, and B cells, our model is able to estimate proportions of naïve, memory, and regulatory CD4+ T cells as well as naïve and memory CD8+ T cells and naïve and memory B cells. Using real and simulated data, we are able to demonstrate that our model is able to reliably estimate proportions of these cell types and subtypes. In studies with DNA methylation data from Illumina's HumanMethylation450k arrays, our estimates will be useful both for testing for associations of cell type and subtype composition with phenotypes of interest as well as for adjustment purposes to prevent confounding in epigenetic association studies. Additionally, our method can be easily adapted for use with whole genome bisulfite sequencing (WGBS) data or any other genome-wide methylation data platform.

RESUMEN

Multiple sclerosis (MS) is a severe disease of the central nervous system (CNS) characterized by autoimmune inflammation and neurodegeneration. Historically, damage to the CNS was thought to be mediated predominantly by activated pro-inflammatory T cells. B cell involvement in the pathogenesis of MS was solely attributed to autoantibody production. The first clues for the involvement of antibody-independent B cell functions in MS pathology came from positive results in clinical trials of the B cell-depleting treatment rituximab in patients with relapsing-remitting (RR) MS. The survival of antibody-secreting plasma cells and decrease in T cell numbers indicated the importance of other B cell functions in MS such as antigen presentation, costimulation, and cytokine production. Rituximab provided us with an example of how clinical trials can lead to new research opportunities concerning B cell biology. Moreover, analysis of the antibody-independent B cell functions in MS has gained interest since these trials. Limited information is present on the effects of current immunomodulatory therapies on B cell functions, although effects of both first-line (interferon, glatiramer acetate, dimethyl fumarate, and teriflunomide), second-line (fingolimod, natalizumab), and even third-line (monoclonal antibody therapies) treatments on B cell subtype distribution, expression of functional surface markers, and secretion of different cytokines by B cells have been studied to some extent. In this review, we summarize the effects of different MS-related treatments on B cell functions that have been described up to now in order to find new research opportunities and contribute to the understanding of the pathogenesis of MS.

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Little is known on the role of distinct B-cell subtypes in human malignancies. We have recently performed a multiplex characterization of B cells in patient-derived tumor-associated tissues, documenting the activation and antigen-driven differentiation of B cells in metastatic lymph nodes and neoplastic lesions. Here we discuss the role of B lymphocytes as antigen-presenting cells and catalysts of T cell-based immunotherapies in view of these findings.