Abstract

In response to an intracellular infectious agent, the immune system produces a specific cellular response as well as a T cell–dependent Ab response. Precursor T cells differentiate into effector T cells, including Th1 cells, and T follicular helper (TFH) cells. The latter cooperate with B cells to form germinal centers and induce the formation of Ab-forming plasmacytes. One major focal point for control of T cell differentiation is the transcription factor BCL6. In this study, we demonstrated that the Bcl6 gene is regulated by FOXO1-binding, cis-acting sequences located in a highly conserved region of the first Bcl6 intron. In both mouse and human T cells, deletion of the tandem FOXO1 binding sites increased the expression of BCL6 and enhanced the proportion of TFH cells. These results reveal a fundamental control point for cellular versus humoral immunity.

Footnotes

This work was supported by The Chancellor’s Associates Chair in the Biological Sciences and by National Institutes of Health/National Institute of Allergy and Infectious Diseases Grant R01AI103440 to S.M.H.

Stephen M. Hedrick is a Distinguished Fellow of AAI.

The online version of this article contains supplemental material.

Abbreviations used in this article:

crRNACRISPR RNAGCgerminal centerLCMVlymphocytic choriomeningitis virusMFImean fluorescence intensitysgRNAsingle guide RNATEFT effectorTFHT follicular helperUCSDUniversity of California, San DiegoVSVvesicular stomatitis virusWTwild-typeReceived August 9, 2021.Accepted July 7, 2022.Copyright © 2022 by The American Association of Immunologists, Inc.