IgD+IgM– B cells mount immune responses that exhibit altered antibody repertoire

IgM and IgD expression during B cell development and differentiation is strictly and developmentally controlled. Although studies have suggested subtle differences in B cell activation, tolerance, and affinity maturation when antigens ligate cell membrane IgM or IgD, the mechanisms that may explain these differences remain unknown and no drastic differences in immune responses have been reported in mice whose B cells selectively lack IgM or IgD. We now show that the antibody repertoire in IgM(-/-) mice is dramatically altered during the primary response to phosphorylcholine. In IgM(-/-) mice, B cells that are activated and differentiate into antibody-forming cells and germinal center B cells express VH genes other than the T15 genes that dominate in wild-type mice. The kinetics of the antigen-specific IgD primary antibody response in IgM(-/-) mice appears similar to that of IgG, but not to that of IgM in wild-type mice. Thus, our studies demonstrate that differences in the roles played by IgM and IgD in regulating the responsiveness and differentiation of B lymphocytes can have major biological consequences during adaptive immune responses.