title: The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6.
abstract: 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 thePou2af1gene, 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 theBcl6andBtlapromoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 andBTLA, 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.
authors.affiliation: Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Stauss
authors.affiliation: Department of Physiological Chemistry, Department of Oto-Rhino-Laryngology Head and Neck Surgery, University of Ulm, Ulm, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Brunner
authors.affiliation: Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Berberich-Siebelt
authors.affiliation: Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Uta E
authors.initials: UE
authors.lastname: Höpken
authors.affiliation: Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
authors.affiliation: Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany g.mueller@mdc-berlin.de.
authors.forename: Gerd
authors.initials: G
authors.lastname: Müller
mesh_terms: D000818:Animals; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007114:Immunization; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011401:Promoter Regions, Genetic; D051560:Proto-Oncogene Proteins c-bcl-6; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D053655:Receptors, Interleukin-21 / Q000235:genetics / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: C488868:BTLA protein, mouse; C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; C490424:Pou2af1 protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D011971:Receptors, Immunologic; D053655:Receptors, Interleukin-21; D019947:Receptors, Interleukin-6; D015534:Trans-Activators
keywords: Pou2af1; T cell differentiation; follicular T helper cells; germinal center; humoral immunity