Abstract
Abstract IgM is an antibody class common to all vertebrates that plays a primary role in host defences against infection. Binding of IgM with an antigen initiates the complement cascade, accelerating cellular and humoral immune responses. However, the functional role of the Fc receptor for IgM in such immune responses remains obscure. Here we show that mice deficient in Fcα/μR, an Fc receptor for IgM expressed on B cells and follicular dendritic cells (FDCs), had enhanced germinal center formation and affinity maturation and memory induction of IgG3+ B cells after immunization with T-independent (TI) antigens. Moreover, Fcα/μR-deficient mice showed prolonged antigen retention by marginal zone B (MZB) cells and FDCs. In vitro studies demonstrated that interaction of the IgM immune complex with Fcα/μR partly suppressed TI antigen retention by MZB cells. We further showed that downregulation of complement receptor (CR)1 and CR2 or complement deprivation by in vivo injection with anti-CR1/2 antibody or cobra venom factor attenuated antigen retention by MZB cells and GC formation after immunization with TI antigens in Fcα/μR-/-_mice. Taken together, these results suggest that Fcα/μR negatively regulates TI antigen retention by MZB cells and FDCs, leading to suppression of humoral immune responses against T-independent antigens.
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