The IgM Fc receptor, FCMR, promotes B cell development and modulates antigen-driven immune responses (176.9)

Abstract FCMR is a Fc receptor specific for pentameric IgM expressed at high levels by B cells. Although circulating IgM has profound effects on responses to pathogens, autoimmunity and B cell homeostasis, the biologic consequences of its binding to FCMR are poorly understood. We interrogated FCMR contributions to B cell function by studying mice lacking FCMR. FCMR transcripts are expressed at highest levels by follicular (FO) B cells and at much lower levels by developing B cells and other mature B cell subsets. FCMR-deficient mice have reduced numbers of developing B cells, splenic FO and peritoneal B-2 cells, but increased levels of peritoneal B-1a cells and autoantibodies. Following immunization, germinal center B cell and plasma cell numbers are increased. FCMR-deficient B cells are resistant to apoptosis induced by BCR ligation. Our studies demonstrate that FCMR functions are critical for B cell homeostasis, the prevention of autoreactive B cells and responsiveness to antigenic challenge.