FAS EXPRESSION AND APOPTOSIS IN HUMAN B-CELLS

Mechanisms of B cell apoptosis are critical in reducing aberrant B cel l proliferations such as those that arise in autoimmune disease and in B cell malignancies. The physiologic interaction of CD4+ helper T cel ls and B lymphocytes has been extensively studied over the past two de cades. Although CD4+ T cells are considered primarily to offer positiv e costimulatory signals for B cell differentiation into active immunog lobulin-secreting cells, recent studies have shown that CD4+ T cells a re crucial in downregulating the humoral immune response. In the cours e of cognate interaction between CD40 ligand (CD40L)-bearing CD4+ T ce lls and CD40-expressing germinal center B cells, CD40 ligation results in augmented Fas expression at the B cell surface. Like CD40L, Fas li gand is expressed on activated CD4+ Th1 cells and when bound to Fas re ceptor on the B cell surface, initiates an apoptotic signal in that ce ll. Thus, CD4+ T cells limit the growth of autologous germinal center B cells by first inducing Fas expression and then instigating a death signal via Fas ligand. In this work, we will consider these observatio ns about CD4+ T-cell-induced, Fas-mediated B cell death in the context of other factors that affect apoptosis in B cells, normal and maligna nt.