B-CELL ACTIVATION BY CROSS-LINKING OF SURFACE IGM OR LIGATION OF CD40INVOLVES ALTERNATIVE SIGNAL PATHWAYS AND RESULTS IN DIFFERENT B-CELL PHENOTYPES

Treatment of small resting B cells with soluble F(ab')(2) fragments of anti-IgM, an analogue of T-independent type 2 antigens, induced activ ation characterized by proliferation and the expression of surface CD5 . In contrast, B cells induced to proliferate in response to thymus-de pendent inductive signals provided by either fixed activated T-helper 2 cells or soluble CD40 ligand-CD8 (CD40L) recombinant protein display ed elevated levels of CD23 (Fc(epsilon)II receptor) and no surface CD5 . Treatment with anti-IgM and CD40L induced higher levels of prolifera tion and generated a single population of B cells coexpressing minimal amounts of CD5 and only a slight elevation of CD23. Anti-IgM- but not CD40L-mediated activation was highly sensitive to inhibition by cyclo sporin A and FK520. Sp-cAMPS, an analogue of cAMP, augmented CD40L and suppressed surface IgM-mediated activation. Taken together these resu lts are interpreted to mean that there is a single population of small resting B cells that can respond to either T-independent type 2 (surf ace IgM)- or T-dependent (CD40)-mediated activation. In response to di fferent intracellular signals these cells are induced to enter alterna tive differentiation pathways.