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

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 ROR gamma t itself and ROR gamma t 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.