IGD CAN LARGELY SUBSTITUTE FOR LOSS OF IGM FUNCTION IN B-CELLS

The mu and delta heavy chains of IgM and IgD, the first antibody isoty pes expressed during bone-marrow B-cell development, are encoded by a common transcription unit. Expression of the mu chain on the surface o f late pre-B cells allows their further development to immature B cell s. Coexpression of the delta chain and emigration of the immature B ce lls to the periphery eventually leads to the development of naive matu re IgM/IgD double-positive cells. Although IgM is important in driving B-cell development(1), the contribution of IgD is not clear. Here we investigate the function of IgD. We generated mice deficient in IgM (I gM(-/-) mice) by deleting the mu. region in embryonic stem cells. IgM- /- mice showed normal B-cell development and maturation, with IgD repl acing membrane-bound and secretory IgM. Moreover, specific B-cell resp onses and isotype class switches occurred during immunization or infec tion. In contrast to mice deficient in B cells, IgM(-/-) mice survived infection with vesicular stomatitis virus by developing neutralizing immunoglobulins, but they were more susceptible than wild-type control s with delayed specific immunoglobulin responses. These data lead us t o conclude that IgD is largely able to substitute for IgM functions.