Regulation of Humoral Immune Responses and B Cell Tolerance by the IgM Fc Receptor (FcμR)

Immunoglobulin (Ig) M is the first antibody isotype produced during an immune response and is critical for host defense against infections. Recent studies have revealed that IgM also plays an important role in immune regulation and immunological tolerance. Mice lacking secretory IgM not only exhibit impaired production of antigen-specific IgG and are more susceptible to bacterial and viral infections, but also produce autoantibodies and are prone to develop autoimmune diseases. For many years, IgM has been thought to function predominantly by binding to antigen and activating complement (C') system. It is now clear that IgM can also elicit its function through the IgM Fc receptor (FcμR). In this chapter, we will review the role of FcμR in B cell development, maturation, survival and activation, antibody production, host defense against bacterial and viral infections, and B cell tolerance. We will also discuss the relative contribution of IgM-C' and IgM-FcμR pathways in humoral immune responses. Finally, we will discuss the possible involvement of FcμR in human chronic lymphocytic leukemia.