title: The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells.
abstract: The transcription factor BATF controls the differentiation of interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) by regulating expression of the transcription factor RORγt itself and RORγt target genes such as Il17. Here we report the mechanism by which BATF controls in vivo class-switch recombination (CSR). In T cells, BATF directly controlled expression of the transcription factors Bcl-6 and c-Maf, both of which are needed for development of follicular helper T cells (T(FH) cells). Restoring T(FH) cell activity to Batf(-/-) T cells in vivo required coexpression of Bcl-6 and c-Maf. In B cells, BATF directly controlled the expression of both activation-induced cytidine deaminase (AID) and of germline transcripts of the intervening heavy-chain region and constant heavy-chain region (I(H)-C(H)). Thus, BATF functions at multiple hierarchical levels in two cell types to globally regulate switched antibody responses in vivo.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ise
authors.forename: Masako
authors.initials: M
authors.lastname: Kohyama
authors.forename: Barbara U
authors.initials: BU
authors.lastname: Schraml
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.forename: Bjoern
authors.initials: B
authors.lastname: Schwer
authors.forename: Uttiya
authors.initials: U
authors.lastname: Basu
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Oltz
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; D002352:Carrier Proteins; C551587:Cmip protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D023201:CD40 Ligand; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase