Unique signaling properties of B cell antigen receptor in mature and immature B cells: Implications for tolerance and activation

Immature B cells display increased sensitivity to tolerance induction compa red with their mature counterparts. The molecular mechanisms underlying the se differences are poorly defined. In this study, we demonstrate unique mat uration stage-dependent differences in B cell Ag receptor (BCR) signaling, including BCR-mediated calcium mobilization responses. Immature B cells dis play greater increases in intracellular calcium concentrations following Ag stimulation. This has consequences for the induction of biologically relev ant responses: immature B cells require lower Ag concentrations for activat ion than mature B cells, as measured by induction of receptor editing and C D86 expression, respectively. BCR-induced tyrosine phosphorylation of CD79a , Lyn, B cell linker protein, and phospholipase C gamma2 is enhanced in imm ature B cells and they exhibit greater capacitative calcium entry in respon se to Ag. Moreover, B cell linker protein, Bruton's tyrosine kinase, and ph ospholipase C gamma2, which are crucial for the induction of calcium mobili zation responses, are present at similar to3-fold higher levels in immature B cells, potentially contributing to increased mobilization of calcium. Co nsistent with this possibility, we found that the previously reported lack of inositol-1,4,5-triphosphate production in immature B cells may be explai ned by enhanced inositol-1,4,5-triphosphate breakdown. These data demonstra te that multiple mechanisms guarantee increased Ag-induced mobilization of calcium in immature B cells and presumably ensure elimination of autoreacti ve B cells from the repertoire.