Work

Interleukin-4-mediated Protection of Primary B Cells from Apoptosis through Stat6-dependent Up-regulation of Bcl-xL

Year: 2002

Type: article

Abstract: Apoptosis is an integral aspect of B lymphocyte development and homeostasis and is regulated by the engagement of antigen costimulatory and cytokine receptors. Although it is well established that interleukin 4 (IL-4) is a potent anti-apoptotic cytokine for B lymphocytes, little is known about the IL-4-induced molecular events regulating cell survival. Stat6 is rapidly activated after IL-4 stimulation, but its role in B lymphocyte apoptosis has not been explored. In this report we demonstrate that Stat6 is a critical signaling molecule for IL-4 in protecting primary B cells from passive and Fas-induced cell death. We show that expression of the Bcl-2 family member, Bcl-xL, is induced maximally by IL-4 and anti-IgM/IL-4 in a Stat6-dependent manner. Additionally, we demonstrate that bcl-xL transcription is likely to be directly activated through a Stat6 binding site in the bcl-xL-flanking region. Finally, reconstitution of Stat6-deficient splenic B cells with Bcl-xL was able to protect those cells from Fas-induced cell death. These results suggest that the anti-apoptotic activity of IL-4 in B cells is mediated through the activation of Stat6 and subsequent transcription of Bcl-xL.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m201207200

Authors: Andrea L. Wurster, Vikki L. Rodgers, Morris F. White, Thomas L. Rothstein, Michael J. Grusby

Institutions: Harvard University, Joslin Diabetes Center, Howard Hughes Medical Institute, Boston University, Boston Medical Center

Language: English

Topic: Cytokine Signaling Pathways and Interactions

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430