Article

The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Nature Immunology (Impact Factor: 24.97). 06/2011; 12(6):536-43. DOI: 10.1038/ni.2037
Source: PubMed

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.

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    • "For example, signal transducer and activator of transcription 6 (Stat6), which is activated by IL-4, binds Region I located upstream of the promoter, and both Stat6 and TGF-b-activated Smad3 and Smad4 bind Region IV located 9 Kb upstream of the Aicda promoter [26]. In addition, paired box protein 5 (Pax5) and E2A proteins bind Region II within the first intron [26] [62], and the AP1 family transcription factor BATF binds Region III located 17 Kb downstream of the promoter [63]. These transcription factors likely interplay with NF-kB, HoxC4 and Sp1/Sp3 at the promoter and enhancer elements, probably through long-range DNA interactions, to mediate Aicda induction by primary CSR-inducing stimuli and cytokines. "
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    • "Recent data highlighted the critical role for the AP-1 family factor BATF in B cells: deletion of this transcription factor induced a dramatic decrease in germline transcription of all acceptor switch regions (Ise et al., 2011), leading to a phenotype close to the complete deletion of the whole 3'RR. Interestingly, chromatin immunoprecipitation experiments showed BATF binding to both I promoters (Ig2b, Ig2a and Ia) and 3'IgH enhancers hs3b, hs1-2, hs3b and hs4 (Ise et al., 2011). "
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