The role of bcl-xL in CD40-mediated rescue from anti-μ-induced apoptosis in WEHI-231 B lymphoma cells

✍ Scribed by Michael S. K. Choi; Lawrence H. Boise; Alexander R. Gottschalk; José Quintans; Craig B. Thompson; Gerry G. B. Klaus

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 725 KB
• Volume: 25
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830250533

✦ Synopsis

The role of bcl-xL in CD40-mediated rescue from anti-y-induced apoptosis in WEHI-231 B lymphoma cells

The phenotypically immature B cell lymphoma WEHI-231 undergoes apoptotic cell death when cultured with anti-immunoglobulin (Ig) antibodies, via a bcl-Zindependent mechanism. We have therefore studied the role of the bcl-Zrelated protein bcl-x in controlling cell death in WEHI-231. We find that overexpression of the long form of bcl-x (bcl-xL) renders these cells refractory to anti-Ig-induced cell death. Stimulation of WEHI-231 via CD40 has similar protective effects. We show here that ligation of CD40 rapidly induces the appearance of the bcl-xL protein in WEHI-231, while stimulation via sIgM, sIgD, CDS or CD4S receptors, or with phorbol esters plus ionomycin does not. WEHI-231 cells also rapidly undergo massive apoptosis following culture with thapsigargin, a specific inhibitor of the Ca2+ -ATPase of the endoplasmic reticulum: this is also reversed by anti-CD40, or by overexpression of bcl-xL.We, therefore, conclude that bcl-xL plays a key role in the regulation of antigen receptor-mediated apoptosis via CD40 in WEHI-231. In addition, the fact that this protein is not induced in WEHI-231 in response to phorbol dibutyrate plus ionomycin points to a fundamental signaling defect in these cells, which could conceivably be a reflection of their immature, apoptosis-susceptible phenotype.