EXPRESSION OF CD40 INDUCES NEURAL APOPTOSIS

The tumor necrosis factor receptor superfamily includes 12 members, so me of which (e.g., tumor necrosis factor receptor I and FAS) induce ce ll death triggered by ligand binding, Another member of the superfamil y, the neurotrophin receptor p75(NTR), induces neural apoptosis, with apoptosis being inhibited by binding of ligand to the receptor, As suc h, it is a candidate for the mediation of neurotrophin dependence, Her e, we show that CD40, a superfamily member that is closely related to p75(NTR), also induces neural apoptosis, but apoptosis is inhibited by binding of the G28-5 monoclonal antibody to CD40, These results provi de further support for a model in which some members of the tumor necr osis factor receptor superfamily induce apoptosis triggered by ligand binding, whereas other members may, at least under certain conditions, induce apoptosis in the absence of ligand binding, with apoptosis bei ng inhibited by binding of ligand or monoclonal antibody. (C) 1997 Wil ey-Liss,Inc.