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Brian T. Gaudette Neal N. Iwakoshi Lawrence H. Boise 《The Journal of biological chemistry》2014,289(34):23629-23640
Although it is known that the unfolded protein response (UPR) plays a significant role in the process of plasma cell differentiation, the contribution of the individual sensors of the UPR to this process remains unclear. In this study we examine the death signals and compensatory survival signals activated during B cell activation and the first stages of plasma cell differentiation. During in vitro differentiation of both primary murine B cells and the Bcl1 cell line, we demonstrate that in addition to activation of the physiological UPR, changes in the expression of several Bcl-2 proteins occur, which are consistent with a lowering of the apoptotic threshold of the cell. Specifically, we observed decreased expression of Bcl-2 and Mcl-1 and increased expression of the proapoptotic protein Bim. However, these changes were countered by Bcl-xL induction, which is necessary to protect differentiating cells both from ER stress-induced death by tunicamycin and from the death signals inherent in differentiation. Consistent with differentiating cells becoming dependent on Bcl-xL for survival, the addition of ABT-737 resulted in apoptosis in differentiating cells through the inhibition of sequestration of Bim. Confirming this result, differentiation in the context of RNAi-mediated Bcl-xL knockdown also induced apoptosis. This cell death is C/EBP homologous protein (CHOP)-dependent, connecting these events to the UPR. Thus plasma cell differentiation proceeds through a Bcl-xL-dependent intermediate. 相似文献
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Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells 总被引:1,自引:0,他引:1
VanDussen KL Carulli AJ Keeley TM Patel SR Puthoff BJ Magness ST Tran IT Maillard I Siebel C Kolterud Å Grosse AS Gumucio DL Ernst SA Tsai YH Dempsey PJ Samuelson LC 《Development (Cambridge, England)》2012,139(3):488-497
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