IgM-mediated signaling is required for the development of a normal B cell memory response.

Mature B cells co-express both IgM and IgD types of antigen receptors before activation. Our earlier work has shown that the co-expression of IgD and IgM plays an important role in regulating the composition of antibody repertoire during a primary immune response. However, the roles of these two B cell receptors in the development of B cell memory responses remain unclear. The present study shows that during the secondary immune response to (4-hydroxy-3-nitrophenyl)acetyl (NP), IgM-/- mice secreted significant amount of NP-specific IgD antibodies. The kinetics of antigen-specific IgD antibodies produced in IgM-/- mice was similar to that of IgM antibodies in wild type mice during the secondary response. However, the production of antigen-specific class-switched antibodies in IgM-/- mice was significantly reduced compared to that in wild type mice, particularly at the early phase of the memory response. In addition, germinal center (GC) reaction was significantly diminished in IgM-/- mice after secondary challenge with soluble antigen. Nevertheless, affinity maturation of antibodies appears largely intact in IgM-/- mice during memory response. Thus, our studies demonstrate that IgM-mediated signaling plays an important role in the development of efficient B cell memory responses.