title: B7-H4 reverse signaling induces the apoptosis of EBV-transformed B cells through Fas ligand up-regulation.
abstract: B7-H4 has an inhibitory effect on immune responses via the down-regulation of T cell-mediated immunity, but how the engagement of B7-H4 molecules by counter molecules affects the signaling mechanism of the B7-H4-expressing cells is poorly defined. In this study, we found that B7-H4 expression was enhanced on B cells infected with Epstein-Barr virus (EBV) and that triggering of these molecules induced apoptosis of EBV-transformed B cells. Engagement of B7-H4 initially increased intracellular level of ROS, which then induced the expression of FasL. Engagement of B7-H4 subsequently provoked Fas-mediated and caspase-dependent apoptosis in association with cytochrome c and AIF, and EndoG was released from the mitochondria on EBV-transformed B cells. These results suggest that B7-H4 may be a potential therapeutic target for EBV involved malignancy diseases.
authors.affiliation: Department of Anatomy and Tumor Immunology, Inje University College of Medicine, 633-165 Kaekum-2-dong, Jin-gu, Busan 614-735, Republic of Korea.
authors.forename: Hyunkeun
authors.initials: H
authors.lastname: Song
authors.forename: Gabin
authors.initials: G
authors.lastname: Park
authors.forename: Yeong-Seok
authors.initials: YS
authors.lastname: Kim
authors.forename: Indo
authors.initials: I
authors.lastname: Hur
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Kim
authors.forename: Jeoung Whan
authors.initials: JW
authors.lastname: Ryu
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Cho
authors.forename: In-Hak
authors.initials: IH
authors.lastname: Choi
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Hur
mesh_terms: D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D018122:B7-1 Antigen / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; D019014:fas Receptor / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D018122:B7-1 Antigen; D053222:Fas Ligand Protein; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; D019014:fas Receptor; D045304:Cytochromes c; D020169:Caspases