Xie, Markus M.Koh, Byung-HeeHollister, KristinWu, HaoSun, JieKaplan, Mark H.Dent, Alexander L.2017-08-022017-08-022017-07Xie, M. M., Koh, B. H., Hollister, K., Wu, H., Sun, J., Kaplan, M. H., & Dent, A. L. (2017). Bcl6 promotes follicular helper T‐cell differentiation and PD‐1 expression in a Blimp1‐independent manner in mice. European Journal of Immunology, 47 (7), 1136-1141. http://dx.doi.org/10.1002/eji.201747034https://hdl.handle.net/1805/13693The transcription factors Bcl6 and Blimp1 have opposing roles in the development of the follicular helper T (TFH) cells: Bcl6 promotes and Blimp1 inhibits TFH-cell differentiation. Similarly, Bcl6 activates, while Blimp1 represses, expression of the TFH-cell marker PD-1. However, Bcl6 and Blimp1 repress each other's expression, complicating the interpretation of the regulatory network. Here we sought to clarify the extent to which Bcl6 and Blimp1 independently control TFH-cell differentiation by generating mice with T-cell specific deletion of both Bcl6 and Blimp1 (double conditional KO [dcKO] mice). Our data indicate that Blimp1 does not control TFH-cell differentiation independently of Bcl6. However, a population of T follicular regulatory (TFR) cells developed independently of Bcl6 in dcKO mice. We have also analyzed regulation of IL-10 and PD-1, two genes controlled by both Bcl6 and Blimp1, and observed that Bcl6 regulates both genes independently of Blimp1. We found that Bcl6 positively regulates PD-1 expression by inhibiting the ability of T-bet/Tbx21 to repress Pdcd1 transcription. Our data provide a novel mechanism for positive control of gene expression by Bcl6, and illuminate how Bcl6 and Blimp1 control TFH-cell differentiation.en-USPublisher Policyfollicular helper T cellsBcl6Blimp1Article