Intrinsic function of STAT3 in B cells is to promote B cell proliferation and maturation

Abstract

Abstract We previously showed that STAT3 promotes T cell survival by restraining unbridled activation and proliferation of T cells (J Biol Chem. 286:30888–97). We also showed that STAT3 regulates Th17 differentiation and the loss of STAT3 in CD4+ T cells prevents development of experimental autoimmune diseases (J Immunol. 180:6070–6). However, the intrinsic and extrinsic functions of STAT3 in B cells are not well understood. In this study, we have generated mice lacking STAT3 in CD19+ B cells and investigated the functions of STAT3 in B cells. Targeted deletion of stat3 in the conditional STAT3KO mouse strain (CD19-CRE-STAT3KO) was verified by Western blot analysis by showing loss of STAT3 expression in CD19+ B cells. We further show by lymphocyte proliferation assays and cell cycle analysis that the CD19-STAT3KO mice proliferated less compared to WT counterparts. Moreover, compared to the development of WT B cells, the STAT3KO mice contained a significantly higher percentage of immature B cells. These results suggest that STAT3 might exhibit diametrically opposite effects in B and T cells; Whereas STAT3 promotes B cell proliferation, STAT3 promotes T-cell survival and inhibits T cell activation/proliferation through up-regulation of Class O Forkhead Transcription Factors. In summary, our study reveals for the first time that STAT3 is required for B cell maturation.