NF-ATc2 induces apoptosis in Burkitt's lymphoma cells through signaling via the B cell antigen receptor

Eisaku Kondo, Akira Harashima, Takami Takabatake, Hideo Takahashi, Yoshinobu Matsuo, Tadashi Yoshino, Kunzo Orita, Tadaatsu Akagi

Research output: Contribution to journalReview articlepeer-review

28 Citations (Scopus)

Abstract

Cross-linking of the B cell antigen receptor (BCR) with an anti-IgM antibody has been shown to induce dramatic apoptosis in type I Burkitt's lymphoma (BL) cells. However, the apoptotic mechanism triggered via BCR remains unknown. Here we reports a mechanism of BCR ligation-induced apoptosis involving protein phosphatase calcineurin and its specific substrate, transcriptional factor NF-AT. In response to BCR cross-linking, endogenous calcineurin was rapidly activated, and this facilitated nuclear translocation of NF-ATc2, a subtype of NF-AT members. Interestingly, nuclear-imported NF-ATc2 functioned pro-apoptotically in BL cells. The effect of NF-ATc2 was efficiently blocked with FK506, which prevented its nuclear translocation through inactivation of calcineurin. In addtion, TR3 induction during BCR cross-linking was reduced by FK506 and the VIVIT peptide, which is a highly selective inhibitor for NF-AT. This strongly suggests that activation of NF-ATc2 by calcineurin is essential for TR3 recruitment, and that TR3 can be considered as a candidate for death effector in BCR-mediated apoptosis. Therefore, NF-ATc2 plays a crucial role in BCR-mediated apoptosis in type I BL, providing greater insight into unique BL characteristics through BCR signaling.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalEuropean Journal of Immunology
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 1 2003

Keywords

  • Apoptosis
  • B cell receptor
  • Burkitt's lymphoma
  • NF-AT
  • TR3

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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