Bcl6 mediates the development of T follicular helper cells

Roza I. Nurieva; Yeonseok Chung; Gustavo J. Martinez; Xuexian O. Yang; Shinya Tanaka; Tatyana D. Matskevitch; Yi Hong Wang; Chen Dong

doi:10.1126/science.1176676

Bcl6 mediates the development of T follicular helper cells

Roza I. Nurieva, Yeonseok Chung, Gustavo J. Martinez, Xuexian O. Yang, Shinya Tanaka, Tatyana D. Matskevitch, Yi Hong Wang, Chen Dong

Research output: Contribution to journal › Article › peer-review

1147 Citations (Scopus)

Abstract

A fundamental function of CD4+ helper (T_H) cells is the regulation of B cell-mediated humoral immunity. Development of T follicular helper (T_FH) cells that provide help to B cells is mediated by the cytokines interleukin-6 and interleukin-21 but is independent of T_H1, T_H2, and T_H17 effector cell lineages. Here, we characterize the function of Bcl6, a transcription factor selectively expressed in T_FH cells. Bcl6 expression is regulated by interleukin-6 and interleukin-21. Bcl6 overexpression induced T_FH-related gene expression and inhibited other T_H lineage cell differentiation in a DNA binding-dependent manner. Moreover, Bcl6 deficiency in T cells resulted in impaired T_FH cell development and germinal center reactions, and altered production of other effector T cell subsets. Our data thus illustrate that Bcl6 is required for programming of T_FH cell generation.

Original language	English
Pages (from-to)	1001-1005
Number of pages	5
Journal	Science
Volume	325
Issue number	5943
DOIs	https://doi.org/10.1126/science.1176676
Publication status	Published - 2009
Externally published	Yes

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@article{53ce3285413d4abea78179ce82677614,

title = "Bcl6 mediates the development of T follicular helper cells",

abstract = "A fundamental function of CD4+ helper (TH) cells is the regulation of B cell-mediated humoral immunity. Development of T follicular helper (TFH) cells that provide help to B cells is mediated by the cytokines interleukin-6 and interleukin-21 but is independent of TH1, TH2, and TH17 effector cell lineages. Here, we characterize the function of Bcl6, a transcription factor selectively expressed in TFH cells. Bcl6 expression is regulated by interleukin-6 and interleukin-21. Bcl6 overexpression induced TFH-related gene expression and inhibited other TH lineage cell differentiation in a DNA binding-dependent manner. Moreover, Bcl6 deficiency in T cells resulted in impaired TFH cell development and germinal center reactions, and altered production of other effector T cell subsets. Our data thus illustrate that Bcl6 is required for programming of TFH cell generation.",

author = "Nurieva, {Roza I.} and Yeonseok Chung and Martinez, {Gustavo J.} and Yang, {Xuexian O.} and Shinya Tanaka and Matskevitch, {Tatyana D.} and Wang, {Yi Hong} and Chen Dong",

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doi = "10.1126/science.1176676",

language = "English",

volume = "325",

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journal = "Science",

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publisher = "American Association for the Advancement of Science",

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T1 - Bcl6 mediates the development of T follicular helper cells

AU - Nurieva, Roza I.

AU - Chung, Yeonseok

AU - Martinez, Gustavo J.

AU - Yang, Xuexian O.

AU - Tanaka, Shinya

AU - Matskevitch, Tatyana D.

AU - Wang, Yi Hong

AU - Dong, Chen

PY - 2009

Y1 - 2009

N2 - A fundamental function of CD4+ helper (TH) cells is the regulation of B cell-mediated humoral immunity. Development of T follicular helper (TFH) cells that provide help to B cells is mediated by the cytokines interleukin-6 and interleukin-21 but is independent of TH1, TH2, and TH17 effector cell lineages. Here, we characterize the function of Bcl6, a transcription factor selectively expressed in TFH cells. Bcl6 expression is regulated by interleukin-6 and interleukin-21. Bcl6 overexpression induced TFH-related gene expression and inhibited other TH lineage cell differentiation in a DNA binding-dependent manner. Moreover, Bcl6 deficiency in T cells resulted in impaired TFH cell development and germinal center reactions, and altered production of other effector T cell subsets. Our data thus illustrate that Bcl6 is required for programming of TFH cell generation.

AB - A fundamental function of CD4+ helper (TH) cells is the regulation of B cell-mediated humoral immunity. Development of T follicular helper (TFH) cells that provide help to B cells is mediated by the cytokines interleukin-6 and interleukin-21 but is independent of TH1, TH2, and TH17 effector cell lineages. Here, we characterize the function of Bcl6, a transcription factor selectively expressed in TFH cells. Bcl6 expression is regulated by interleukin-6 and interleukin-21. Bcl6 overexpression induced TFH-related gene expression and inhibited other TH lineage cell differentiation in a DNA binding-dependent manner. Moreover, Bcl6 deficiency in T cells resulted in impaired TFH cell development and germinal center reactions, and altered production of other effector T cell subsets. Our data thus illustrate that Bcl6 is required for programming of TFH cell generation.

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DO - 10.1126/science.1176676

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SP - 1001

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JO - Science

JF - Science

IS - 5943

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Bcl6 mediates the development of T follicular helper cells

Abstract

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