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Gutzeit, Cindy; Chen, Kang; Cerutti, Andrea
European Journal of Immunology, July 2018, Volume: 48, Issue: 7Journal Article
IgD emerged soon after IgM at the time of inception of the adaptive immune system. Despite its evolutionary conservation from fish to humans, the specific functions of IgD have only recently begun to be elucidated. Mature B cells undergo alternative mRNA splicing to express IgD and IgM receptors with identical antigenic specificity. The enigma of dual IgD and IgM expression has been tackled by several recent studies showing that IgD helps peripheral accumulation of physiologically autoreactive B cells through its functional unresponsiveness to self‐antigens but prompt readiness against foreign antigens. IgD achieves this balance by attenuating IgM‐mediated anergy while promoting specific responses to multimeric non‐self‐antigens. Additional research has clarified how and why certain mucosal B cells become plasmablasts or plasma cells specializing in IgD secretion. In particular, the microbiota has been shown to play an important role in driving class switch‐mediated replacement of IgM with IgD. Secreted IgD appears to enhance mucosal homeostasis and immune surveillance by “arming” myeloid effector cells such as basophils and mast cells with IgD antibodies reactive against mucosal antigens, including commensal and pathogenic microbes. Here we will review these advances and discuss their implications in humoral immunity in human and mice. IgD and IgM engagement by microbial antigens induces B cell entry into a germinal center pathway that generates plasma cells secreting IgG,IgA, IgE or IgD. In self‐reactive B cells, engagement of IgM by self‐antigen induces an IgD‐modulated anergy‐inducing program that is shut off by microbial antigens cross‐reactive with self‐epitopes.
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