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Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1555-60. doi: 10.1073/pnas.1017729108. Epub 2011 Jan 4.

14-3-3sigma regulates B-cell homeostasis through stabilization of FOXO1.

Author information

  • 1Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C1.

Erratum in

  • Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6689. Hermeking, Heiko [added]; Vogelstein, Bert [added].
  • Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15849.

Abstract

14-3-3σ regulates cytokinesis and cell cycle arrest induced by DNA damage but its role in the immune system is unknown. Using gene-targeted 14-3-3σ-deficient (i.e., KO) mice, we studied the role of 14-3-3σ in B-cell functions. Total numbers of B cells were reduced by spontaneous apoptosis of peripheral B cells. Upon B-cell antigen receptor engagement in vitro, KO B cells did not proliferate properly or up-regulate CD86. In response to T cell-independent antigens, KO B cells showed poor secretion of antigen-specific IgM. This deficit led to increased lethality of KO mice after vesicular stomatitis virus infection. KO B cells showed elevated total FOXO transcriptional activity but also increased FOXO1 degradation. Coimmunoprecipitation revealed that endogenous 14-3-3σ protein formed a complex with FOXO1 protein. Our results suggest that 14-3-3σ maintains FOXO1 at a consistent level critical for normal B-cell antigen receptor signaling and B-cell survival.

PMID:
21205887
[PubMed - indexed for MEDLINE]
PMCID:
PMC3029705
Free PMC Article

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