Opposing roles of IgM and IgD in <scp>BCR</scp>‐induced B‐cell survival

Yasuda, Shoya; Sun, Jiping; Zhou, Yang; Wang, Yan-Qing; Lü, Qing; Yamamura, Masatoshi; Wang, Ji‐Yang

doi:10.1111/gtc.12635

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…IgD is an important antibody secreted by B lymphocytes, and elevated surface IgD and decreased surface IgM expression are hallmarks of nonreactive B cells present in human peripheral blood and peripheral lymphoid organs of mice [56]. Similarly, Shoya Yasuda and colleagues have suggested that B cell survival response to BCR stimulation was negatively correlated with IgD levels [57]. Combined with our results, we boldly speculated that IDA may impact not only the proliferation of immune cells, but also their activity.…”

Section: Discussionsupporting

confidence: 78%

Causal relationships between immune cells and iron deficiency anemia: a bidirectional Mendelian randomization study

xu,

li,

Liu

et al. 2024

Preprint

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Background Observational studies have shown a potential link between immune factors and the risk of iron deficiency anemia (IDA), yet the causal relationship between immune cells and IDA remains enigmatic. Herein, we used Mendelian randomization (MR) to assess whether this association is causal. Methods We selected IDA genetic variants, including 8376 samples and 9810691 single nucleotide polymorphisms, and immune cells from a large open genome-wide association study (GWAS) for a bidirectional MR study. The primary method was inverse variance weighting (IVW), and auxiliary analyses were MR-Egger, weighted median, simple mode and weighted mode. The reliability of the results was subsequently verified by heterogeneity and sensitivity analysis. Results IVW method showed that 19 types of immune cells may be the risk factors of IDA, whereas 15 types of immune cells are the protective factors of IDA. Reverse MR analysis suggested that immune cells from upstream etiology of IDA are not involved in follow-up immune activities. Next, we selected 731 immune cell types as the results. The research revealed that IDA may result in a rise in 23 kinds of immune cells and a reduction in 12 kinds of immune cells. In addition, sensitivity analysis demonstrated no evidence of heterogeneity or horizontal pleiotropy. Conclusions From a genetic standpoint, our study suggests that specific immune cells are involved in the occurrence of IDA. Inversely, IDA may also contribute to immune dysfunction, thus guiding future clinical investigations.

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Section: Discussionsupporting

confidence: 78%

Causal relationships between immune cells and iron deficiency anemia: a bidirectional Mendelian randomization study

xu,

li,

Liu

et al. 2024

Preprint

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“…It is likely that IgD-deficient B cells have disrupted organization of nanoclusters as stimulatory co-receptors cannot be confined to IgD nanoclusters and may thus easily associate with IgM resulting in accelerated activation of IgD-deficient B cells. It was recently reported that IgM and IgD-class BCR play opposing roles in B cell survival and that the IgD-class BCR negatively affects B cell activation and differentiation ( 34 ). Here, we show that the IgD-class BCR prevents rapid B cell activation and IgM antibody secretion, which is in agreement with the notion that IgD is likely a negative regulator of B cell activation.…”

Section: Discussionmentioning

confidence: 99%

Primary Immune Responses and Affinity Maturation Are Controlled by IgD

et al. 2021

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Mature B cells co-express IgM and IgD B cell antigen receptors (BCR) on their surface. While IgM BCR expression is already essential at early stages of development, the role of the IgD-class BCR remains unclear as most B cell functions appeared unchanged in IgD-deficient mice. Here, we show that IgD-deficient mice have an accelerated rate of B cell responsiveness as they activate antibody production within 24h after immunization, whereas wildtype (WT) animals required 3 days to activate primary antibody responses. Strikingly, soluble monovalent antigen suppresses IgG antibody production induced by multivalent antigen in WT mice. In contrast, IgD-deficient mice were not able to modulate IgG responses suggesting that IgD controls the activation rate of B cells and subsequent antibody production by sensing and distinguishing antigen-valences. Using an insulin-derived peptide we tested the role of IgD in autoimmunity. We show that primary autoreactive antibody responses are generated in WT and in IgD-deficient mice. However, insulin-specific autoantibodies were detected earlier and caused more severe symptoms of autoimmune diabetes in IgD-deficient mice as compared to WT mice. The rapid control of autoimmune diabetes in WT animals was associated with the generation of high-affinity IgM that protects insulin from autoimmune degradation. In IgD-deficient mice, however, the generation of high-affinity protective IgM is delayed resulting in prolonged autoimmune diabetes. Our data suggest that IgD is required for the transition from primary, highly autoreactive, to secondary antigen-specific antibody responses generated by affinity maturation.

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“…The elevated expression of surface IgD and downregulation of IgM receptors are hallmarks of anergic naïve B cells that contain autoreactive receptors both in mice and human peripheral blood [ 17 , 18 ]. In these cells, studies have shown that surface IgD restrains the response to self-antigens and promotes the accumulation of anergic B cells [ 19 , 20 ]. Furthermore, the loss of anergic B cells has been observed in some autoimmune diseases [ 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

IgD+IgM− B Cells in Common Variable Immunodeficiency

Kasahara,

Gupta

2024

Pathogens

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Common variable immunodeficiency (CVID) is the most frequent form of primary hypogammaglobulinemia in adults. In addition to recurrent infections and respiratory manifestations, CVID patients may present several non-infection complications such as autoimmune diseases. The mechanisms that lead to immune dysregulation in CVID are not completely understood. Given the role of IgD on naïve B cells in the maintenance of tolerance and secreted IgD in the respiratory mucosa, we evaluated the frequency of IgD+ naïve and IgD+ memory B cells in CVID patients. Here, no differences were observed in the percentages and proliferative responses of anergic IgD+IgM−CD27− B cells between CVID patients, with or without autoimmune disease, and the control group. Interestingly, in the compartment of memory B cells, the percentage of IgD+IgM− cells was higher only in CVID patients with allergic rhinitis/allergic asthma. Our results may indicate that anergic IgD+IgM−CD27− B cells may not be compromised in our CVID cohort. However, IgD+IgM− memory B cells may play a role in the immunopathogenesis of allergic rhinitis/allergic asthma in CVID patients. Further studies are needed to better understand the participation of IgD+IgM− memory B cells in the immunopathogenesis of allergic rhinitis/allergic asthma in CVID patients.

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Opposing roles of IgM and IgD in BCR‐induced B‐cell survival

Cited by 4 publications

References 33 publications

Causal relationships between immune cells and iron deficiency anemia: a bidirectional Mendelian randomization study

Causal relationships between immune cells and iron deficiency anemia: a bidirectional Mendelian randomization study

Primary Immune Responses and Affinity Maturation Are Controlled by IgD

IgD+IgM− B Cells in Common Variable Immunodeficiency

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