Increase in Bcl-2 level promoted by CD40 ligation correlates with inhibition of B cell apoptosis induced by vacuolar type H+-ATPase inhibitor

Sumio Akifusa, Masahiro Ohguchi, Takeyoshi Koseki, Kazuhiko Nara, Ichiro Semba, Kenji Yamato, Nobuo Okahashi, Ramon Merino, Gabriel Núñez, Nobuhiro Hanada, Tadamichi Takehara, Tatsuji Nishihara

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

We have previously demonstrated that cell death of WEHI-231 cells induced by specific inhibitors of vacuolar type H+-ATPase (V-ATPase) occurs through apoptosis. CD40 is involved in regulating activation, differentiation, and apoptosis of B cells. Here we show that the CD40 ligation rescues WEHI-231 cells from apoptotic cell death induced by a specific V-ATPase inhibitor, concanamycin A. CD40 signaling with anti-CD40 antibody resulted in the induction of Bcl-2 and Bcl-XL proteins in WEHI-231 cells. Constitutive expression of Bcl-2 but not Bcl-XL inhibited concanamycin A-induced apoptosis. These findings suggest that the expression of Bcl-2 mediated through CD40 signaling rescues the apoptotic cell death induced by blockade of V-ATPase. Interestingly, the acidification of intracellular acidic compartments was completely inhibited when WEHI-231 cells were cultured with concanamycin A, even in the presence of anti-CD40 antibody. In addition, apoptosis in WEHI-231 cells induced by concanamycin A was strongly suppressed when cultured with imidazole, a cell-permeable base, suggesting that apoptosis induced by concanamycin A is preceded by intraacidification.

Original languageEnglish
Pages (from-to)82-89
Number of pages8
JournalExperimental Cell Research
Volume238
Issue number1
DOIs
Publication statusPublished - 1998 Jan 10
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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