CD40-and HLA-DR-mediated cell death pathways share a lot of similarities but differ in their use of ADP-ribosyltransferase activities

CD40 and HLA-DR molecules are two major components of the immune system, an d their engagement on several cell types leads to various cellular events t hat modulate cell function, In this study, we demonstrate that signaling vi a these molecules leads to a rapid B cell death. CD40-mediated cell death w as mainly observed in Epstein-Barr virus (EBV)-transformed B cell lines, wh ereas, HLA-DR-induced response can be triggered in normal activated B cells as well as in EBV-transformed B cell lines, Cell death induced via both mo lecules does not require de novo protein synthesis, but involves the integr ity of the cytoskeleton. The sensitivity of CD40- and HLA-DR-mediated cell death to various inhibitors is very similar to that previously reported for tumor necrosis factor receptor (TNFR)- and Fas-triggered apoptosis; howeve r, caspases leading to poly(ADP-ribose) polymerase cleavage are not implica ted in this response. Both B cell death forms do not involve Fas-Fas ligand and TNF-TNFR systems, but require LFA-l-independent cell-cell interactions mediated by still undefined molecules. Although CD40- and HLA-DR-mediated cell death appears to follow a common pathway, inhibitors of poly- and mono -ADP-ribosyltransferase activity differentially affect these responses. Def ining the molecules involved in CD40- and HLA-DR-mediated death will provid e a possible interrelation between the different B cell death programs that can lead to a better comprehension of regulation of B cell functions.