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Author Notes:

To whom correspondence should be addressed: Lawrence H. Boise, Dept. of Hematology and Medical Oncology, Dept. of Cell Biology, and Winship Cancer Institute, Emory University, 1365C Clifton Rd. NE, Ste. C4012, Atlanta, GA 30322. Tel.: 404-778-4724; Fax: 404-778-5530; E-mail: lboise@emory.edu.

We thank Ned Waller and Kasia Darlak for assistance with mouse spleens and the Boise laboratory for critical feedback on the data.


Research Funding:

This work was supported, in whole or in part, by National Institutes of Health Grants R01 CA127910 and R01 CA129968 as well as funding from the T. J. Martell Foundation (to L. H. B.).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Apoptosis
  • Bcl-2 Proteins
  • Differentiation
  • ER Stress
  • Lymphocyte
  • UPR
  • Plasma Cell
  • MCL-1
  • XBP-1
  • ATF6

Bcl-x(L) Protein Protects from C/EBP Homologous Protein (CHOP)-dependent Apoptosis during Plasma Cell Differentiation


Journal Title:

Journal of Biological Chemistry


Volume 289, Number 34


, Pages 23629-23640

Type of Work:

Article | Final Publisher PDF


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-x L 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.

Copyright information:

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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