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PMID: 19628815 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Bcl6 mediates the development of T follicular helper cells.

Science (New York, N.Y.) ·Vol. 325 ·No. 5943 ·2009-08-21 ·Pages 1001-5

Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, Matskevitch TD, Wang YH, Dong C

Abstract

A fundamental function of CD4+ helper T (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 TH1, TH2, and TH17 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.

MeSH Terms
Animals Antibody Formation B-Lymphocytes/immunology Cell Differentiation Cell Lineage Cytokines/immunology,metabolism DNA-Binding Proteins/deficiency,genetics,metabolism Germinal Center/cytology,immunology Immunoglobulins/biosynthesis Interleukin-6/immunology,metabolism Interleukins/immunology,metabolism Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Transgenic Mutation Proto-Oncogene Proteins c-bcl-6 RNA, Messenger/genetics,metabolism T-Lymphocyte Subsets/cytology,immunology T-Lymphocytes, Helper-Inducer/cytology,immunology Transcription Factors/genetics,metabolism
Chemicals
Bcl6 protein, mouse Cytokines DNA-Binding Proteins Immunoglobulins Interleukin-6 Interleukins Proto-Oncogene Proteins c-bcl-6 RNA, Messenger Transcription Factors interleukin-21
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Nurieva Roza I
Department of Immunology, M. D. Anderson Cancer Center, Houston, TX 77030, USA. rnurieva@mdanderson.org
Chung Yeonseok
Martinez Gustavo J
Yang Xuexian O
Tanaka Shinya
Matskevitch Tatyana D
Wang Yi-Hong
Dong Chen
References (16)
16 references, click to expand
  1. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages.
    Immunity. 2008 Jul 18;29(1):138-49 PMID: 18599325
  2. Follicular B helper T cells in antibody responses and autoimmunity.
    Nat Rev Immunol. 2005 Nov;5(11):853-65 PMID: 16261173
  3. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs.
    Immunity. 2008 Jul 18;29(1):44-56 PMID: 18585065
  4. T follicular helper (TFH) cells in normal and dysregulated immune responses.
    Annu Rev Immunol. 2008;26:741-66 PMID: 18173374
  5. Follicular helper T cells: lineage and location.
    Immunity. 2009 Mar 20;30(3):324-35 PMID: 19303387
  6. Cytokine-secreting follicular T cells shape the antibody repertoire.
    Nat Immunol. 2009 Apr;10(4):385-93 PMID: 19252490
  7. Germinal centres: role in B-cell physiology and malignancy.
    Nat Rev Immunol. 2008 Jan;8(1):22-33 PMID: 18097447
  8. Point mutations in BCL6 DNA-binding domain reveal distinct roles for the six zinc fingers.
    Biochem Biophys Res Commun. 2003 Jan 10;300(2):391-6 PMID: 12504096
  9. Control of inflammation, cytokine expression, and germinal center formation by BCL-6.
    Science. 1997 Apr 25;276(5312):589-92 PMID: 9110977
  10. Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching.
    Mol Cell Biol. 1999 Oct;19(10):7264-75 PMID: 10490661
  11. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma.
    Immunity. 2008 Jan;28(1):29-39 PMID: 18164222
  12. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells.
    Nat Immunol. 2009 Feb;10(2):167-75 PMID: 19098919
  13. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function.
    Nature. 2008 May 8;453(7192):236-40 PMID: 18368049
  14. A fundamental role for interleukin-21 in the generation of T follicular helper cells.
    Immunity. 2008 Jul 18;29(1):127-37 PMID: 18602282
  15. The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation.
    Nat Genet. 1997 Jun;16(2):161-70 PMID: 9171827
  16. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.
    Cell. 2006 Sep 22;126(6):1121-33 PMID: 16990136
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1176676
Email
rnurieva@mdanderson.org
Published
2009-08-21
Epub
2009-00-23
Pages
1001-5
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2857334
Subset
IM
Grants
NIAID NIH HHS · R01 AI050746-05 · United States
NIAID NIH HHS · R01 AI050746 · United States
NIAMS NIH HHS · R01 AR050772-08 · United States
NIAMS NIH HHS · R01 AR050772-07 · United States
NIAMS NIH HHS · R01 AR050772 · United States
NIAID NIH HHS · R01 AI083761 · United States
NIAID NIH HHS · R01 AI050761-06 · United States
NIAID NIH HHS · R01 AI050761-07A1 · United States
NIAID NIH HHS · R01 AI050761 · United States
NIAID NIH HHS · R01 AI050761-05 · United States
Corrections
CommentIn
PMID: 19696339
External Links
PubMed source DOI: 10.1126/science.1176676 PMC Full Text View journal details
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