CD80 (B7.1) and CD86 (B7.2) induce EBV-transformed B cell apoptosis through the Fas/FasL pathway

Park,Ga  Bin; Kim,Yeong  Seok; Lee,Hyun-Kyung; Cho,Dae-Ho; Kim,Daejin; Hur,Dae   Young

doi:10.3892/ijo.2013.2091

CD80 (B7.1) and CD86 (B7.2) induce EBV-transformed B cell apoptosis through the Fas/FasL pathway

Authors:
- Ga Bin Park
- Yeong Seok Kim
- Hyun-Kyung Lee
- Dae-Ho Cho
- Daejin Kim
- Dae Young Hur
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Affiliations: Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea, Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea, Department of Life Science, Sookmyung Women's University, Yongsan-gu, Yongsan-ku, Seoul 140-742, Republic of Korea
Published online on: September 5, 2013 https://doi.org/10.3892/ijo.2013.2091
Pages: 1531-1540

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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.

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