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

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

doi:10.1038/ni.2037

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

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

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293 Scopus citations

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 ROR3t itself and ROR3t 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.

Original language	English
Pages (from-to)	536-543
Number of pages	8
Journal	Nature immunology
Volume	12
Issue number	6
DOIs	https://doi.org/10.1038/ni.2037
State	Published - Jun 2011

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@article{ce5c22e2853e4912941439c9a98d2045,

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 (TH 17 cells) by regulating expression of the transcription factor ROR3t itself and ROR3t 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.",

author = "Wataru Ise and Masako Kohyama and Schraml, {Barbara U.} and Tingting Zhang and Bjoern Schwer and Uttiya Basu and Alt, {Frederick W.} and Jun Tang and Oltz, {Eugene M.} and Murphy, {Theresa L.} and Murphy, {Kenneth M.}",

note = "Funding Information: We thank T. Honjo (Kyoto University) for Aicda−/− mice; and D. Bhattacharya (Washington University) for retroviruses Bcl-6-GFP RV and CD40L-GFP RV. Supported by the Howard Hughes Medical Institute (K.M.M.).",

year = "2011",

month = jun,

doi = "10.1038/ni.2037",

language = "English",

volume = "12",

pages = "536--543",

journal = "Nature immunology",

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AU - Ise, Wataru

AU - Kohyama, Masako

AU - Schraml, Barbara U.

AU - Zhang, Tingting

AU - Schwer, Bjoern

AU - Basu, Uttiya

AU - Alt, Frederick W.

AU - Tang, Jun

AU - Oltz, Eugene M.

AU - Murphy, Theresa L.

AU - Murphy, Kenneth M.

N1 - Funding Information: We thank T. Honjo (Kyoto University) for Aicda−/− mice; and D. Bhattacharya (Washington University) for retroviruses Bcl-6-GFP RV and CD40L-GFP RV. Supported by the Howard Hughes Medical Institute (K.M.M.).

PY - 2011/6

Y1 - 2011/6

N2 - The transcription factor BATF controls the differentiation of interleukin 17 (IL-17)-producing helper T cells (TH 17 cells) by regulating expression of the transcription factor ROR3t itself and ROR3t 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.

AB - The transcription factor BATF controls the differentiation of interleukin 17 (IL-17)-producing helper T cells (TH 17 cells) by regulating expression of the transcription factor ROR3t itself and ROR3t 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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JO - Nature immunology

JF - Nature immunology

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

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