Programmed cell death by bcl-2-dependent and independent mechanisms in B lymphoma cells.

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Abstract
Programmed cell death (PCD) or apoptosis is a common form of cellular demise during embryogenesis, tumorigenesis and clonal selection in the immune system. The bcl‐2 proto‐oncogene has been recently implicated as a potential physiological regulator of the PCD pathway. Gene transfer studies have shown that overexpression of bcl‐2 blocks apoptosis mediated by several stimuli in cultured cell lines and promotes the survival of B and T lymphocytes in transgenic mice. However, it remains unclear whether under normal conditions bcl‐2 is responsible for controlling cell death. We have investigated the role of bcl‐2 in the antimembrane IgM (mIgM)‐induced apoptotic death of WEHI‐231 B cell lymphoma, a model that mimics clonal deletion of immature B cells by antigen. Signalling of mIgM receptors triggered downregulation of both bcl‐2 RNA and protein, and induced apoptosis in WEHI‐231 B cells. This effect appeared to be specific since (i) the levels of beta 2‐microglobulin and beta‐actin RNA remain unchanged and (ii) signalling of the apoptosis‐resistant B cell lymphoma line BAL‐17 with anti‐mu was not associated with downregulation of bcl‐2 RNA. However, stable expression of bcl‐2 by transfection did not rescue WEHI‐231 B cells from apoptosis, yet WEHI‐231 cells overexpressing bcl‐2 were more resistant to programmed cell death induced by heat‐shock.(ABSTRACT TRUNCATED AT 250 WORDS)