RNAseq of WT and Stat6 knockout Tfh21 and Tfh4 cells

We report that Stat6-driven gene transcription regulates the transition from Tfh21 to Tfh4 cells, suppressing IL-21 production and promoting IL-4 secretion. We identified a cis-enhancer in the second intron of Il21 as a regulator of Tfh cell cytokine transition, via an effect of Stat6 on chromatin accessibility with repression of Il21 transcription. We conclude that Stat6 is necessary for coordinated regulation of IL-21 and IL-4 production by Tfh cells, leading to appropriate maturation of the germinal center B cell response. Overall design: Examination of 2 different Tfh populations from Stat6 intact and knockout cells.