IL-4 AND ANTI-CD40 PROTECT AGAINST FAS-MEDIATED B-CELL APOPTOSIS AND INDUCE B-CELL GROWTH AND DIFFERENTIATION

Most T(h)2 clones, when activated, produce IL-4 and express CD40 ligan d (CD40L) on their cell surface. Therefore, they can induce growth and differentiation of B cells by cognate help, In contrast, activated T( h)1 clones, which produce IFN-gamma and express both CD40L and Fas lig and (Fast) on their cell surface, often induce B cell apoptotic cell d eath, To understand the mechanism by which T(h)2 cells can induce a ce ll growth and differentiation in the presence of Fast-positive cells, we stimulated a cells with IL-4, anti-IgM and/or anti-CD40 in the pres ence of anti-Fas, We report here that addition of anti-Fas strongly in hibited anti-CD40-induced B cell proliferation without affecting anti- IgM-induced a cell proliferation, Furthermore we showed that stimulati on of B cells with anti-CD40 induced the expression of Fas molecules o n the B cells (similar to 30%) and rendered them highly sensitive to a nti-fas-mediated apoptotic cell death, Indeed, over 23% of anti-CD40-s timulated B cells showed hypodiploid DNA after being incubated with an ti-Fas, while <2% of anti-CD40-stimulated B cells showed hypodiploid D NA after being incubated with medium alone, We also showed that IL-4 e nhanced expression of Fas on anti-CD40-induced a cells (similar to 50% ), although co-stimulation with anti-CD40 and IL-4 protected B cells f rom anti-fas-mediated apoptotic cell death and induced their growth an d differentiation, Our present result might suggest that T(h)2 cells c ould dominate over Fast-positive T(h)1 cells by production of CD40L an d IL-4, which in combination induce antibody production and inhibit th e T(h)1 cell-mediated immune response.