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The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6
Author(s) -
Stauss Dennis,
Brunner Cornelia,
BerberichSiebelt Friederike,
Höpken Uta E,
Lipp Martin,
Müller Gerd
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201591459
Subject(s) - biology , bcl6 , germinal center , transcription factor , coactivator , microbiology and biotechnology , transcriptional regulation , cellular differentiation , t cell , cancer research , immunology , b cell , immune system , genetics , gene , antibody
Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long‐term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4 + T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by the Pou2af1 gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate the Bcl6 and Btla promoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 and BTLA , thereby controlling the pool size and composition of the Tfh compartment in a T cell‐intrinsic manner. Our data indicate that T cell‐expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell‐dependent B‐cell responses.