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

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Abstract
The phenotypically immature B cell lymphoma WEHI‐231 undergoes apoptotic cell death when cultured with anti‐immunoglobulin (Ig) antibodies, via a bcl‐2‐independent mechanism. We have therefore studied the role of the bcl‐2‐related 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, CD5 or CD45 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.