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

ABSTRACT: 14-3-3? regulates cytokinesis and cell cycle arrest induced by DNA damage but its role in the immune system is unknown. Using gene-targeted 14-3-3?-deficient (i.e., KO) mice, we studied the role of 14-3-3? 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 14-3-3? protein formed a complex with FOXO1 protein. Our results suggest that 14-3-3? maintains FOXO1 at a consistent level critical for normal B-cell antigen receptor signaling and B-cell survival.

SUBMITTER: Su YW 

PROVIDER: S-EPMC3029705 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature