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Publication : Bach2 Controls T Follicular Helper Cells by Direct Repression of Bcl-6.

First Author  Lahmann A Year  2019
Journal  J Immunol Volume  202
Issue  8 Pages  2229-2239
PubMed ID  30833348 Mgi Jnum  J:291417
Mgi Id  MGI:6444956 Doi  10.4049/jimmunol.1801400
Citation  Lahmann A, et al. (2019) Bach2 Controls T Follicular Helper Cells by Direct Repression of Bcl-6. J Immunol 202(8):2229-2239
abstractText  T follicular helper (Tfh) cells are a specialized T cell subset that regulates the long-lived production of highly specific Abs by B cells during the germinal center (GC) reaction. However, the transcriptional network sustaining the Tfh cell phenotype and function is still incompletely understood. In this study, we identify the transcription factor Bach2 as a central negative regulator of Tfh cells. Ectopic overexpression of Bach2 in murine Tfh cells resulted in a rapid loss of their phenotype and subsequent breakdown of the GC response. Low Bach2 expression levels are required to maintain high expression of the signature cytokine IL-21, the coinhibitory receptor TIGIT and the transcriptional repressor Bcl-6. In stark contrast to the regulatory network in GC B cells, Bach2 in Tfh cells is not coexpressed with Bcl-6 at high levels to inhibit the antagonizing factor Blimp-1, but suppresses Bcl-6 by direct binding to the promoter. These data reveal that by replacing an activating complex of Batf and Irf-4 at the Bcl-6 promoter, Bach2 regulates the transcriptional network of Tfh cells in a different way, as in GC B cells.
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