title: Bcl6 mediates the development of T follicular helper cells.
abstract: A fundamental function of CD4+ helper T (T(H)) cells is the regulation of B cell-mediated humoral immunity. Development of T follicular helper (T(FH)) cells that provide help to B cells is mediated by the cytokines interleukin-6 and interleukin-21 but is independent of TH1, TH2, and TH17 effector cell lineages. Here, we characterize the function of Bcl6, a transcription factor selectively expressed in T(FH) cells. Bcl6 expression is regulated by interleukin-6 and interleukin-21. Bcl6 overexpression induced T(FH)-related gene expression and inhibited other T(H) lineage cell differentiation in a DNA binding-dependent manner. Moreover, Bcl6 deficiency in T cells resulted in impaired T(FH) cell development and germinal center reactions, and altered production of other effector T cell subsets. Our data thus illustrate that Bcl6 is required for programming of T(FH) cell generation.
authors.affiliation: Department of Immunology, M. D. Anderson Cancer Center, Houston, TX 77030, USA. rnurieva@mdanderson.org
authors.forename: Roza I
authors.initials: RI
authors.lastname: Nurieva
authors.forename: Yeonseok
authors.initials: Y
authors.lastname: Chung
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Martinez
authors.forename: Xuexian O
authors.initials: XO
authors.lastname: Yang
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tatyana D
authors.initials: TD
authors.lastname: Matskevitch
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007136:Immunoglobulins / Q000096:biosynthesis; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000098546:Interleukin-21
chemical_list: C490010:Bcl6 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D015850:Interleukin-6; D007378:Interleukins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D014157:Transcription Factors; D000098546:Interleukin-21