IL21 is a cytokine that is most highly expressed by a specific subpopulation of CD4-positive T cells termed T follicular helper (TFH) cells. IL21 is normally produced by TFH in response to bacterial or viral infections or immunization with various vaccines. Normally, IL21 promotes the activation and differentiation of antigen-specific B cells to passage germinal centers to become memory B cells or long-lived plasma cells that secrete specific antibodies at high levels. How B cells contribute to the process of TFH maturation and function has been unclear. To understand the role of IL21 in autoimmunity, we studied autoimmune 564Igi mice that cary an autoreactive B cell receptor. Unexpectedly, these mice were found to develop a high incidence of B cell lineage neoplasms and accesses. Both these manifestations as well as signs of autoimmunity were essentially eliminated in jic depleted of gut microbiota by treatment with antibiotics. Characterizing the binding of different immunoglobulin classes to receptors for their Fc portions has greatly expanded our understandings of their functions in vivo. Our recent studies of the recently described IgM Fc receptor demonstrated that it is required for normal B cell differentiation and homeostasis, responses to antigenic challenge and prevention of autoimmunity. Since a number of different names had we been used to describe the protein and the gene encoding it, we contributed to the development of a consensus nomenclature that resulted in the use of FCRM for the gene and FCRM for the protein. We also published a review on the features and functions of FCRM.
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