Acquisition of surface IgD fails to protect from tolerance-induction. Both surface IgM- and surface IgD-mediated signals induce apoptosis of immature murine B lymphocytes.

While mature splenic B cells are surface (s)IgM+ and sIgD+, immature, tolerance-susceptible B cells express sIgM and varying levels of sIgD. Differential expression of sIgD on tolerance-susceptible and resistant B cells suggests that sIgM and sIgD may transmit qualitatively different signals. Alternatively, tolerance sensitivity may be associated with intrinsic differences in sIg signaling, regardless of the isotype engaged. Here, we have exploited a stage of B cell development at which immature, tolerance-sensitive B cells co-express sIgD and sIgM. Using these immature stage B cells to evaluate isotypic differences in the ability to induce activation and deletion, we have found that neither ligation of sIgD nor sIgM is capable of inducing proliferation. Moreover, in contrast to mature B cells, both sIgD and sIgM induce apoptosis by immature stage B cells. Importantly, cross-linking sIgD does not protect immature B cells from sIgM-induced apoptosis. Thus, the differences in tolerance susceptibility of immature and mature B cells must be due to intrinsic developmental rather than isotypic differences in Ag receptor signal transduction.