title: CD80 (B7.1) and CD86 (B7.2) induce EBV-transformed B cell apoptosis through the Fas/FasL pathway.
abstract: CD80 and CD86 expression is strongly regulated in B cells and is induced by various stimuli (e.g., cytokines, ligation of MHC class II and CD40 ligand). Epstein-Barr virus (EBV) infection activates B lymphocytes and transforms them into lymphoblastoid cells. However, the role of CD80 and CD86 in EBV infection of B cells remains unclear. Here, we observed that cross-linking of CD80 and CD86 in EBV-transformed B cells induced apoptosis through caspase-dependent release of apoptosis-related molecules, cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, because Z-VAD-fmk (N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone) and N-acetylcysteine (NAC) blocked apoptosis and disruption of mitochondria. Stimulation of CD80 and CD86 induced expression of Fas ligand (FasL) on EBV-transformed B cells and upregulated Fas and FasL expression in IM-9 cells. Apoptosis through Fas-FasL interactions was blocked by treatment of cells with ZB4, an antagonistic anti-Fas antibody. These results suggest that the co-stimulatory molecules CD80 and CD86 induced by EBV infection stimulate apoptosis of EBV-transformed lymphoblastoid B cells via the Fas/FasL pathway.
authors.affiliation: Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Ga Bin
authors.initials: GB
authors.lastname: Park
authors.forename: Yeong Seok
authors.initials: YS
authors.lastname: Kim
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Cho
authors.forename: Daejin
authors.initials: D
authors.lastname: Kim
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Hur
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D020031:Epstein-Barr Virus Infections / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D053222:Fas Ligand Protein / Q000378:metabolism*; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor