Molecular and functional characteristics of the Fcα/μR, a novel Fc receptor for IgM and IgA

IgM is the first antibody to be produced in a humoral immune response and is a major isotope of natural antibodies and may play an important role in innate immunity. On the other hand, IgA is a secreted antibody at the mucosal membrane such as the gastrointestinal and respiratory tracts and protects from initial invasion of microbes. However, how these antibodies are involved in immunity has been poorly elucidated. We previously identified a novel Fc receptor for IgA and IgM, designated Fc alpha/mu receptor (Fc alpha/mu R), whose gene is closely located at the polymeric immunoglobulin receptor (poly-IgR), also a receptor for IgA and IgM, in the Fc receptor gene cluster on the chromosome 1. In contrast to the the poly-IgR that is expressed on epithelial, but not hematopoietic, cells, Fc alpha/mu R is constitutively expressed on the majority of B lymphocytes and macrophages in the spleen and at the center of the secondary lymphoid follicles. The Fc alpha/mu R mediates endocytosis Staphylococcus aureus/anti-S. aureus IgM antibody immune complexes by B lymphocytes, for which the dileucine motif in the cytoplasmic tail of the mouse Fc alpha/mu R is responsible. These results reveal a new mechanism in the primary stage of immune defense against microbes.