International Immunology, Vol. 11, No. 5, 719-730,
May 1999
© 1999 Japanese Society for Immunology
CD40- and HLA-DR-mediated cell death pathways share a lot of similarities but differ in their use of ADP-ribosyltransferase activities
Centre de Recherche en Rhumatologie et Immunologie, Le Centre Hospitalier de Québec, Pavillon CHUL, 2705 Boulevard Laurier, T1-49, Sainte-Foy, Québec G1V 4G2, Canada
Correspondence to: W. Mourad
CD40 and HLA-DR molecules are two major components of the immune system, and their engagement on several cell types leads to various cellular events that modulate cell function. In this study, we demonstrate that signaling via these molecules leads to a rapid B cell death. CD40-mediated cell death was mainly observed in Epstein–Barr virus (EBV)-transformed B cell lines, whereas, 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 molecules does not require de novo protein synthesis, but involves the integrity 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; however, caspases leading to poly(ADP-ribose) polymerase cleavage are not implicated in this response. Both B cell death forms do not involve Fas–Fas ligand and TNF–TNFR systems, but require LFA-1-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. Defining the molecules involved in CD40- and HLA-DR-mediated death will provide a possible interrelation between the different B cell death programs that can lead to a better comprehension of regulation of B cell functions.
Keywords: apoptosis, B lymphocytes, CD40, MHC class II
Transmitting editor: C. Terhorst
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