Expression of CD40 induces neural apoptosis.

The tumor necrosis factor receptor superfamily includes 12 members, some of which (e.g., tumor necrosis factor receptor I and FAS) induce cell death triggered by ligand binding. Another member of the superfamily, the neurotrophin receptor p75NTR, induces neural apoptosis, with apoptosis being inhibited by binding of ligand to the receptor. As such, it is a candidate for the mediation of neurotrophin dependence. Here, we show that CD40, a superfamily member that is closely related to p75NTR, also induces neural apoptosis, but apoptosis is inhibited by binding of the G28-5 monoclonal antibody to CD40. These results provide further support for a model in which some members of the tumor necrosis 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 being inhibited by binding of ligand or monoclonal antibody.