![Figure 2. Molecular regulation of Tfh development. Tfh development requires the integrated and balanced function of numerous transcription factors. BATF acts proximally by inducing Bcl-6 and c-Maf. Bcl-6 imprints a Tfh fate by suppressing expression and/or function of transcriptional regulators of alternate effector fates (i.e., Tbx21 [Th1], Gata3 [Th2], and Rorc [Th17]), microRNAs that suppress Tfh generation, and Prdm1 (encoding Blimp-1), which directly suppresses Bcl-6. c-Maf contributes to Tfh cells by inducing CXCR5 and IL-21. STAT3-activating cytokines IL-6, IL-21, and IL-27 can also induce c-Maf, and STAT3 can directly induce IL-21. IL-12 induces IL-21 in a STAT3-dependent manner, but it is unknown whether this involves c-Maf or is a direct effect of STAT3. Tfh generation is restricted by Blimp-1, which is induced by IL-2 in a STAT5-dependent manner and blocks Bcl-6 expression, and by T-bet (induced by IL-12), which physically associates with Bcl-6 and prevents Bcl-6–dependent repression.](https://cdn.rupress.org/rup/content_public/journal/jem/209/7/10.1084_jem.20120994/5/jem_20120994_fig2.jpeg?Expires=1770156846&Signature=TxvhIc9UaoXZ0nX1uQiFaser2tWtd88pjy~xes5PIOgiBGhQeZPHSuoMwPxoGjpsY-tt14Wor2a9QUiqUVjA8kNsXE-3Mm7EX1H~eFBidRPVefuSQpf-L8bg8jWBEDdFunuui7eI2ddpcXMhtm3xSCbS6Aa-Zv20tZi3A4dOkp0hlaDGDHJiZ6dJPaA4ZSTnPEs~0--ULlZA1aUpC8AJg4qAuYv-VGBQnfvAeQqXjPoae5XgY1g~x61d7TJt47yNGGWt8X~RqfpByDoxW~pT3ULfQsWzblJYyPfsw~4zjRq-1sBJoKl2J3IXGeg0oA3d2T50KN8FpUdkictZgqHqhw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Molecular regulation of Tfh development. Tfh development requires the integrated and balanced function of numerous transcription factors. BATF acts proximally by inducing Bcl-6 and c-Maf. Bcl-6 imprints a Tfh fate by suppressing expression and/or function of transcriptional regulators of alternate effector fates (i.e., Tbx21 [Th1], Gata3 [Th2], and Rorc [Th17]), microRNAs that suppress Tfh generation, and Prdm1 (encoding Blimp-1), which directly suppresses Bcl-6. c-Maf contributes to Tfh cells by inducing CXCR5 and IL-21. STAT3-activating cytokines IL-6, IL-21, and IL-27 can also induce c-Maf, and STAT3 can directly induce IL-21. IL-12 induces IL-21 in a STAT3-dependent manner, but it is unknown whether this involves c-Maf or is a direct effect of STAT3. Tfh generation is restricted by Blimp-1, which is induced by IL-2 in a STAT5-dependent manner and blocks Bcl-6 expression, and by T-bet (induced by IL-12), which physically associates with Bcl-6 and prevents Bcl-6–dependent repression.
