Abstract
Abstract Recent work has identified a new subset of CD4+ T cells named as T follicular helper (Tfh) cells that are localized in germinal centers and critical in germinal-center formation. Tfh cell differentiation is regulated by IL-6 and IL-21, possibly via STAT3 factor, and Bcl6 is specifically expressed in Tfh cells and required for their lineage specification. In current study, we characterized the role of STAT5 in developmental regulation of Tfh cells. We found that a constitutively active form of STAT5 effectively inhibited Tfh differentiation by suppressing the expression of Tfh-associated factors CXCR5, c-Maf, Bcl6, Batf and IL-21, whereas STAT5 deficiency greatly enhanced Tfh differentiation. In addition, deletion of STAT5 in CD4+ T cells in vivo resulted in enhanced development of Tfh cells and germinal center B cells, and led to an impairment of B cell tolerance, suggesting that STAT5 signaling controls the humoral immunity. This knowledge may help us to find ways to treat antibody-mediated autoimmune diseases.
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