bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes

Differential effects of BCL-2 on survival and proliferation of human B-lymphoma cells following γ-irradiation

“…Bcl-2-expression has been shown previously to protect human B cells from other apoptotic stimuli, including growth/ survival factor withdrawal, antigen receptor crosslinking and Ca 2+ -ionophore treatment Holder et al, 1993;Milner et al, 1992Milner et al, , 1993Wang et al, 1996). Bcl-2 has also been shown to repress apoptosis in response to DNA damage in a variety of systems (Collins et 1996; Sentman et al, 1991;Strasser et al, 1994;Soldatenkov et al, 1996). Interestingly, we noted that the presence of Bcl-2 was not su cient to maintain prolonged resistance to apoptosis and all three Bcl-2 transfectants showed evidence of increased apoptosis by one week after irradiation, with one cell line (CHEP/Bcl-2) showing a markedly high level (up to 60%).…”

“…Exogenous growth/survival factors, such as IFN-g, IL-2, IL-3, IL-4 and IL-7 suppress DNA-damage-induced apoptosis (Canman et al, 1995;Collins et al, 1992;Sangfelt et al, 1996;Seki et al, 1995). Constitutive expression of bcl-2, the prototype survival gene, also promotes survival of cells exposed to radiation and other DNAdamaging agents (Collins et al, 1992;Gilbert et al, 1996;Kyprianou et al, 1997;Lock and Stribinskiene, 1996;Sentman et al, 1991;Strasser et al, 1994;Soldatenkov et al, 1996).…”

NF-κB and the immune response

“…As a consequence, the antiapoptotic properties of NF-kB play a key role in lymphopoiesis. The centrality of its antiapoptotic function is supported in part by the demonstration that most of the requirements for NF-kB during T-cell development can be overcome by transgenic expression of the prototypical antiapoptotic factor Bcl-2 (Sentman et al, 1991). The necessity of NF-kB for lymphopoiesis is strikingly illustrated in human genetic diseases wherein the gene encoding NEMO is inactivated by mutation (see Courtois and Gilmore, 2006).…”

Bcl-2, Bcl-xL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death

“…For example, although B and T lymphocytes from bcl-2 transgenic mice are resistant to numerous cytotoxic agents (McDonnell et al, 1989;Sentman et al, 1991;Strasser et al, 1991aStrasser et al, ,b, 1994a, they remain sensitive to apoptosis induced by activation of the surface receptor Fas/APO-1 (CD95) (Strasser et al, 1995c). Moreover, although bcl-2 transgene expression enhances the survival of immature B and T cells that have failed to receive a survival signal (`death by neglect') (Linette et al, 1994;Strasser et al, 1994b,c), it is an ine ective antidote to`activation induced apoptosis' of lymphocytes bearing autoreactive antigen receptors (Sentman et al, 1991;Strasser et al, , 1994b and does not protect against killing mediated by cytotoxic T cells (Vaux et al, 1992b). This inability of Bcl-2 to antagonise all pathways to physiological cell death is not restricted to lymphocytes, since its overexpression enhances the survival of sensory neurons deprived of NGF, but does not prevent apoptosis of ciliary neurons deprived of ciliary neurotrophic factor (CNTF) (Allsopp et al, 1993).…”