INCREASE IN BCL-2 LEVEL PROMOTED BY CD40 LIGATION CORRELATES WITH INHIBITION OF B-CELL APOPTOSIS INDUCED BY VACUOLAR-TYPE H-ATPASE INHIBITOR()

We have previously demonstrated that cell death of WEHI-231 cells indu ced by specific inhibitors of vacuolar type H+-ATPase (V-ATPase) occur s through apoptosis. CD40 is involved in regulating activation, differ entiation, and apoptosis of B cells. Here we show that the CD40 ligati on rescues WEHI-231 cells from apoptotic cell death induced by a speci fic V-ATPase inhibitor, concanamycin A. CD40 signaling with anti-CD40 antibody resulted in the induction of Bcl-2 and Bcl-XL proteins in WEH I-231 cells, Constitutive expression of Bcl-2 but not Bcl-XL inhibited concanamycin A-induced apoptosis. These findings suggest that the exp ression of Bcl-2 mediated through CD40 signaling rescues the apoptotic cell death induced by blockade of V-ATPase. Interestingly, the acidif ication of intracellular acidic compartments was completely inhibited when WEHI-231 cells were cultured with concanamycin A, even in the pre sence of anti-CD40 antibody. In addition, apoptosis in WEHI-231 cells induced by concanamycin A was strongly suppressed when cultured with i midazole, a cell-permeable base, suggesting that apoptosis induced by concanamycin A is preceded by intraacidification. (C) 1998 Academic Pr ess.