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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / immunology*
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Basic-Leucine Zipper Transcription Factors / metabolism
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CD40 Ligand / genetics
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CD40 Ligand / immunology
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CD40 Ligand / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Carrier Proteins / metabolism
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Cells, Cultured
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Cytidine Deaminase / genetics
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Cytidine Deaminase / metabolism
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Female
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Flow Cytometry
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Gene Expression Profiling
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Germinal Center / immunology
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Germinal Center / metabolism
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Immunoglobulin Class Switching / genetics
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Immunoglobulin Class Switching / immunology*
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Lymphocyte Activation / immunology
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Male
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Mice
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Mice, 129 Strain
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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Proto-Oncogene Proteins c-bcl-6 / genetics
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Proto-Oncogene Proteins c-bcl-6 / immunology
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Proto-Oncogene Proteins c-bcl-6 / metabolism
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Recombination, Genetic
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Basic-Leucine Zipper Transcription Factors
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Batf protein, mouse
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Carrier Proteins
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Cmip protein, mouse
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Proto-Oncogene Proteins c-bcl-6
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CD40 Ligand
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AICDA (activation-induced cytidine deaminase)
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Cytidine Deaminase