Cutting edge: selection of B lymphocyte subsets is regulated by natural IgM.

Natural IgM has a wide range of actions in the immune system. Here we demonstrate that mice lacking serum IgM have an expansion in splenic marginal zone B cells with a proportionately smaller reduction in follicular B cells. The increase in the marginal zone-follicular B cell ratio (and an expansion in peritoneal B1a cells) is fully reversed by administration of polyclonal IgM, but not by two IgM monoclonals. Mice engineered to have a secreted oligoclonal IgM repertoire with an endogenous membrane IgM also exhibited a similar expansion of marginal zone B cells. We propose that natural IgM, by virtue of its polyreactivity, enhances Ag-driven signaling through the B cell receptor and promotes the formation of follicular B cells. These results demonstrate that natural IgM regulates the selection of B lymphocyte subsets.