A NOVEL FUNCTION OF CD40 - INDUCTION OF CELL-DEATH IN TRANSFORMED-CELLS

CD40 is known as an important T-B cell interaction molecule which resc ues B lymphocytes from undergoing apoptosis. Like other receptors of t he tumor necrosis factor (TNF) receptor gene family, CD40 is expressed on cells of different tissue origins including some transformed cells . In contrast to its well-studied effects on B cells, the biological f unctions of CD40 in nonimmune cells remain largely unknown. Here we sh ow that CD40 ligation induces apoptotic cell death in transformed cell s of mesenchymal and epithelial origin. This CD40-mediated cell death seems to use a preformed signaling pathway since it occurs even when p rotein synthesis is blocked. Notably, the CD40 cytoplasmic domain shar es a structural homology with the recently defined ''death domains'' o f the 55-kD TNF receptor (p55TNFR) and Fas. Despite these structural s imilarities, differences are seen in the way phorbol myristate acetate , interleukin 1, TNF, and various metabolic inhibitors influence the c ellular responsiveness to CD40, p55TNFR, and Fas-mediated killing. Our study indicates that CD40 induces cell death by a distinct mechanism.