The Role of BCR Isotype in B-Cell Development and Activation

Surova, Elena; Jumaa, Hassan

doi:10.1016/b978-0-12-800266-7.00003-0

Cited by 6 publications

(5 citation statements)

References 184 publications

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“…And IgG1 and IgA1 were the major Ig classes, accounting for 40.15 and 18.81% of all clonal BCRs, respectively ( Figure 4C ). IgG-expressing B cells have higher plasma cell differentiation ability, thus increasing antibody secretion in response to viral infection [ 39 , 40 ]. Statistics of the gene segments in each isotype showed that IgM and IgD utilized multiple V gene segments, while IgG and IgA showed skewing of different V gene segments ( Figures 4D and E and S5C–H , see Supplementary Data available online at http://bib.oxfordjournals.org/ ).…”

Section: Resultsmentioning

confidence: 99%

Global characterization of B cell receptor repertoire in COVID-19 patients by single-cell V(D)J sequencing

Jin

Zhou

Luo

et al. 2021

Briefings in Bioinformatics

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The world is facing a pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Adaptive immune responses are essential for SARS-CoV-2 virus clearance. Although a large body of studies have been conducted to investigate the immune mechanism in COVID-19 patients, we still lack a comprehensive understanding of the BCR repertoire in patients. In this study, we used the single-cell V(D)J sequencing to characterize the BCR repertoire across convalescent COVID-19 patients. We observed that the BCR diversity was significantly reduced in disease compared with healthy controls. And BCRs tend to skew toward different V gene segments in COVID-19 and healthy controls. The CDR3 sequences of heavy chain in clonal BCRs in patients were more convergent than that in healthy controls. In addition, we discovered increased IgG and IgA isotypes in the disease, including IgG1, IgG3 and IgA1. In all clonal BCRs, IgG isotypes had the most frequent class switch recombination events and the highest somatic hypermutation rate, especially IgG3. Moreover, we found that an IgG3 cluster from different clonal groups had the same IGHV, IGHJ and CDR3 sequences (IGHV4-4-CARLANTNQFYDSSSYLNAMDVW-IGHJ6). Overall, our study provides a comprehensive characterization of the BCR repertoire in COVID-19 patients, which contributes to the understanding of the mechanism for the immune response to SARS-CoV-2 infection.

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Section: Resultsmentioning

confidence: 99%

Global characterization of B cell receptor repertoire in COVID-19 patients by single-cell V(D)J sequencing

Jin

Zhou

Luo

et al. 2021

Briefings in Bioinformatics

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“…The two isotypes bear the same antigenic specificity and differ only in terms of their heavy chains, IgMs carry mu (μ) and IgDs carry delta (δ) heavy chains (7). Most CLL cells express both IgMs and IgDs, (8–10) and several studies characterized the importance of IgM BCRs for CLL cell survival, cell-cycle entry, and proliferation (9, 11–13).…”

Section: Introductionmentioning

confidence: 99%

Functional Differences between IgM and IgD Signaling in Chronic Lymphocytic Leukemia

Hacken

Sivina

Kim

et al. 2016

The Journal of Immunology

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B-cell receptor (BCR) signaling is a central pathogenetic pathway in chronic lymphocytic leukemia (CLL). Most CLL cells express BCRs of IgM and IgD isotypes, but the contribution of these isotypes to functional responses remains incompletely defined. We therefore investigated differences between IgM and IgD signaling in freshly isolated peripheral blood CLL cells and in CLL cells cultured with nurselike cells (NLC), a model that mimics the lymph node microenvironment. IgM signaling induced prolonged activation of ERK kinases, promoted CLL cell survival, CCL3 and CCL4 chemokine secretion, and down-regulation of BCL6, the transcriptional repressor of CCL3. In contrast, IgD signaling induced activation of the cytoskeletal protein HS1, along with F-actin polymerization, which resulted in rapid receptor internalization, and failure to support downstream responses including CLL cell survival and chemokine secretion. IgM and IgD receptor down-modulation, HS1 and ERK activation, chemokine secretion and BCL6 down-regulation were also observed when CLL cells were co-cultured with NLC. The BTK kinase inhibitor ibrutinib effectively inhibited both, IgM and IgD isotype signaling. In conclusion, through a variety of functional readouts, we demonstrate very distinct outcomes of IgM and IgD isotype activation in CLL cells, providing novel insight into the regulation of BCR signaling in CLL.

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“…[2][3][4] During the developmental process, B cells encounter multiple signaling regulations and various cell-fate decisions. 5 Defined stages of committed B-cell precursors include pro-B cells, pre-B cells, and finally immature and mature B cells expressing variable amounts of surface immunoglobulin M (IgM) and other markers. [6][7][8] Although studies on different mouse mutants provided fundamental insights into this process, [7][8][9] the detailed molecular regulation mechanisms of early B-cell development are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Phosphatase Wip1 controls antigen-independent B-cell development in a p53-dependent manner

Chen

et al. 2015

Blood

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Key Points• Wip1 controls antigenindependent B-cell development in the bone marrow via a p53-dependent pathway.• Wip1 is essential to prevent an aging-related decline in B-cell development.Wild-type p53-induced phosphatase 1 (Wip1), a phosphatase previously considered as an oncogene, has been implicated in the regulation of thymus homeostasis and neutrophil maturation. However, the role of Wip1 in B-cell development is unknown. We show that Wip1-deficient mice exhibit a significant reduction of B-cell numbers in the bone marrow, peripheral blood, and spleen. A reciprocal transplantation approach revealed a cell-intrinsic defect in early B-cell precursors caused by Wip1 deficiency. Further experiments revealed that Wip1 deficiency led to a sustained activation of p53 in B cells, which led to increased level of apoptosis in the pre-B-cell compartment. Notably, the impairment of B-cell development in Wip1-deficient mice was completely rescued by genetic ablation of p53, but not p21. Therefore, loss of Wip1 phosphatase induces a p53-dependent, but p21-independent, mechanism that impairs B-cell development by enhancing apoptosis in early B-cell precursors. Moreover, Wip1 deficiency exacerbated a decline in B-cell development caused by aging as evidenced in mice with aging and mouse models with serial competitive bone marrow transplantation, respectively. Our present data indicate that Wip1 plays a critical role in maintaining antigen-independent B-cell development in the bone marrow and preventing an aging-related decline in B-cell development. (Blood. 2015;126(5):620-628)

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The Role of BCR Isotype in B-Cell Development and Activation

Cited by 6 publications

References 184 publications

Global characterization of B cell receptor repertoire in COVID-19 patients by single-cell V(D)J sequencing

Global characterization of B cell receptor repertoire in COVID-19 patients by single-cell V(D)J sequencing

Functional Differences between IgM and IgD Signaling in Chronic Lymphocytic Leukemia

Phosphatase Wip1 controls antigen-independent B-cell development in a p53-dependent manner

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