Primary Immune Responses and Affinity Maturation Are Controlled by IgD.

Timm Amendt, Omar El Ayoubi, Alexandra T Linder, Gabriele Allies, Marc Young, Corinna S Setz, Hassan Jumaa

Frontiers in immunology 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. Copyright © 2021 Amendt, Ayoubi, Linder, Allies, Young, Setz and Jumaa.

Citation

Timm Amendt, Omar El Ayoubi, Alexandra T Linder, Gabriele Allies, Marc Young, Corinna S Setz, Hassan Jumaa. Primary Immune Responses and Affinity Maturation Are Controlled by IgD. Frontiers in immunology. 2021;12:709240