B7-H4 reverse signaling induces the apoptosis of EBV-transformed B cells through Fas ligand up-regulation

Hyunkeun Song, Gabin Park, Yeong Seok Kim, Indo Hur, Hyunjin Kim, Jeoung Whan Ryu, Hyun Kyung Lee, Dae Ho Cho, In Hak Choi, Wang Jae Lee, Dae Young Hur

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)227-237
Number of pages11
JournalCancer letters
Issue number2
Publication statusPublished - 2008 Aug 8
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the SRC/ERC program of MOST/KOSEF (Grant # R11-2005-017-02002-0) and MRC program of KOSEF grant funded by the Korean government (MOST) (R13-2007-023-00000-0), and the 2007 Inje University Research Grant.


  • Apoptosis
  • B cell
  • B7-H4
  • EBV
  • Fas
  • FasL

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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