Alam M K, Davison S, Siddiqui N, Norton J D, Murphy J J
Infection and Immunity Research Group, Division of Life Sciences, King's College London, GB.
Eur J Immunol. 1997 Dec;27(12):3485-91. doi: 10.1002/eji.1830271249.
The human Burkitt lymphoma Ramos B cell line can be induced to undergo apoptosis in response to a variety of different agents, including calcium ionophores, anti-immunoglobulin (Ig) and macromolecular synthesis inhibitors. In addition, following up-regulation of the Fas (CD95) surface receptor by CD40 ligation, these cells also become susceptible to apoptosis induction by Fas ligation. We have previously shown that protection from calcium ionophore- and macromolecular synthesis inhibitor-induced apoptosis by CD40 ligation is associated with a rapid up-regulation of Bcl-xL followed by a more moderate and delayed up-regulation of Bcl-2. We show here that overexpression of Bcl-xL, like Bcl-2, protects Ramos cells from apoptosis induction in response to calcium ionophore, anti-Ig and macromolecular synthesis inhibition. However, in contrast to Bcl-2, ectopic overexpression of Bcl-xL does not rescue from Fas-mediated apoptosis. Thus, in Ramos B cells, the Fas apoptotic pathway exhibits differential sensitivity to inhibition by Bcl-2 family members. These findings also suggest that CD40 signaling provides a switch which renders the cells susceptible to Fas-ligand mediated apoptosis through up-regulation of Fas whilst affording protection from anti-Ig-induced apoptosis through up-regulation of Bcl-xL.
人伯基特淋巴瘤Ramos B细胞系可被多种不同因子诱导发生凋亡，这些因子包括钙离子载体、抗免疫球蛋白（Ig）和大分子合成抑制剂。此外，在通过CD40连接上调Fas（CD95）表面受体后，这些细胞也会变得易于被Fas连接诱导凋亡。我们之前已经表明，CD40连接对钙离子载体和大分子合成抑制剂诱导的凋亡的保护作用与Bcl-xL的快速上调相关，随后是Bcl-2更为适度和延迟的上调。我们在此表明，与Bcl-2一样，Bcl-xL的过表达可保护Ramos细胞免受钙离子载体、抗Ig和大分子合成抑制诱导的凋亡。然而，与Bcl-2不同，Bcl-xL的异位过表达不能挽救Fas介导的凋亡。因此，在Ramos B细胞中，Fas凋亡途径对Bcl-2家族成员的抑制表现出不同的敏感性。这些发现还表明，CD40信号传导提供了一个开关，通过上调Fas使细胞易于受到Fas配体介导的凋亡，同时通过上调Bcl-xL提供对抗Ig诱导的凋亡的保护。
