title: Bcl-xL rescues WEHI 231 B lymphocytes from oxidant-mediated death following diverse apoptotic stimuli.
abstract: Developing lymphocytes undergo extensive cell death during selection of the immune repertoire. We investigated the influence of bcl-xL, a member of the bcl-2 family of apoptosis regulatory genes, on apoptosis in a model system for negative selection in the B lymphoid lineage. Overexpression of bcl-xL in WEHI 231 immature mouse B cells blocked apoptosis triggered by cross-linking of surface IgM. bcl-xL-transfected cells were also resistant to apoptosis following incubation in low serum medium or exposure to gamma-irradiation, the sphingomyelin ceramide, or compounds that increase intracellular levels of oxidants. Remarkably, the addition of antioxidants (catalase, N-acetylcysteine, or pyruvate) alone rescued the native WEHI 231 cells from apoptosis while having only minor effects on the viability of cells overexpressing bcl-xL. Anti-IgM cross-linking, ceramide, and gamma-irradiation treatments elevated intracellular peroxide production, which was prevented by treatment with antioxidants. Cells overexpressing bcl-xL had a similar rise in intracellular oxidants as control cells, indicating that bcl-xL modifies the cell's response to oxidants while having no detectable influence on the endogenous production of oxidants following apoptotic stimuli. These data implicate bcl-xL as a potent death repressor in B lymphocytes and support the hypothesis that bcl-xL regulates survival decisions within susceptible cells by functioning downstream of oxidant production.
authors.affiliation: Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455, USA.
authors.forename: W
authors.initials: W
authors.lastname: Fang
authors.forename: J J
authors.initials: JJ
authors.lastname: Rivard
authors.forename: J A
authors.initials: JA
authors.lastname: Ganser
authors.forename: T W
authors.initials: TW
authors.lastname: LeBien
authors.forename: K A
authors.initials: KA
authors.lastname: Nath
authors.forename: D L
authors.initials: DL
authors.lastname: Mueller
authors.forename: T W
authors.initials: TW
authors.lastname: Behrens
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects*; D002460:Cell Line; D002518:Ceramides / Q000633:toxicity; D005720:Gamma Rays / Q000009:adverse effects; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species / Q000633:toxicity*; D014162:Transfection; D051020:bcl-X Protein
chemical_list: D000975:Antioxidants; C494812:Bcl2l1 protein, mouse; D002518:Ceramides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051020:bcl-X Protein