The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6
Open Access
- 8 March 2016
- journal article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 35 (8), 881-898
- https://doi.org/10.15252/embj.201591459
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 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.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (TR52/B8, BR‐2891/4‐1)
- Fritz Thyssen Stiftung (Az.10.13.2.215)
This publication has 76 references indexed in Scilit:
- Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profileNature Immunology, 2012
- ICOS Receptor Instructs T Follicular Helper Cell versus Effector Cell Differentiation via Induction of the Transcriptional Repressor Bcl6Immunity, 2011
- The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cellsNature Immunology, 2011
- Selective Utilization of Toll-like Receptor and MyD88 Signaling in B Cells for Enhancement of the Antiviral Germinal Center ResponseImmunity, 2011
- Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent ReporterCell, 2010
- Optimal Germinal Center Responses Require a Multistage T Cell:B Cell Adhesion Process Involving Integrins, SLAM-Associated Protein, and CD84Immunity, 2010
- Analysis of Interleukin-21-Induced Prdm1 Gene Regulation Reveals Functional Cooperation of STAT3 and IRF4 Transcription FactorsImmunity, 2009
- The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cellsNature Immunology, 2008
- SAP-controlled T–B cell interactions underlie germinal centre formationNature, 2008
- Polycomb complexes repress developmental regulators in murine embryonic stem cellsNature, 2006