Journal Article

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

Kohyama, Masako, Schraml, Barbara U, Oltz, Eugene M, Murphy, Kenneth M, Basu, Uttiya, Alt, Frederick W, Ise, Wataru, Tang, Jun, Zhang, Tingting, Murphy, Theresa L, Schwer, Bjoern

2011

Overview

The transcription factor BATF is known to control switched antibody responses. Murphy and colleagues show that BATF functions at multiple hierarchical levels in follicular helper T cells and B cells to regulate these responses. 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 .

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/1619/40 / 631/250/1619/554 / 631/250/2152/2498 / 631/45/612/822 / Adaptor Proteins, Signal Transducing / AICDA (Activation-Induced Cytidine Deaminase) / Animals / B cells / B-Lymphocytes - immunology / B-Lymphocytes - metabolism / Basic-Leucine Zipper Transcription Factors - genetics / Basic-Leucine Zipper Transcription Factors - immunology / Basic-Leucine Zipper Transcription Factors - metabolism / Biomedical and Life Sciences / Biomedicine / Carrier Proteins - genetics / Carrier Proteins - immunology / Carrier Proteins - metabolism / CD40 Ligand - genetics / CD40 Ligand - immunology / CD40 Ligand - metabolism / Cells, Cultured / Cytidine Deaminase - genetics / Cytidine Deaminase - metabolism / Female / Flow Cytometry / Gene expression / Gene Expression Profiling / Germinal Center - immunology / Germinal Center - metabolism / Immunoglobulin Class Switching - genetics / Immunoglobulin Class Switching - immunology / Immunology / Infectious Diseases / Lymphocyte Activation - immunology / Male / Mice / Mice, 129 Strain / Mice, Inbred BALB C / Mice, Inbred C57BL / Mice, Inbred Strains / Mice, Knockout / Oligonucleotide Array Sequence Analysis / Physiological aspects / Proto-Oncogene Proteins c-bcl-6 - genetics / Proto-Oncogene Proteins c-bcl-6 - immunology / Proto-Oncogene Proteins c-bcl-6 - metabolism / Recombination, Genetic / T cells / T-Lymphocytes - immunology / T-Lymphocytes - metabolism / Transcription factors