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PMID: 19608860 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation.

Science (New York, N.Y.) ·Vol. 325 ·No. 5943 ·2009-08-21 ·Pages 1006-10

Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B, Dent AL, Craft J, Crotty S

Abstract

Effective B cell-mediated immunity and antibody responses often require help from CD4+ T cells. It is thought that a distinct CD4+ effector T cell subset, called T follicular helper cells (T(FH)), provides this help; however, the molecular requirements for T(FH) differentiation are unknown. We found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo T(FH) differentiation and T cell help to B cells in mice. In contrast, the transcription factor Blimp-1, an antagonist of Bcl6, inhibits T(FH) differentiation and help, thereby preventing B cell germinal center and antibody responses. These findings demonstrate that T(FH) cells are required for proper B cell responses in vivo and that Bcl6 and Blimp-1 play central but opposing roles in T(FH) differentiation.

MeSH Terms
Animals Antibody Formation Arenaviridae Infections/immunology B-Lymphocytes/immunology CD4-Positive T-Lymphocytes/cytology,immunology Cell Differentiation Cell Lineage Cytokines/metabolism DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation Germinal Center/cytology,immunology Lymphocyte Activation Lymphocytic choriomeningitis virus/immunology Mice Mice, Inbred C57BL Mice, Transgenic Positive Regulatory Domain I-Binding Factor 1 Proto-Oncogene Proteins c-bcl-6 RNA, Messenger/genetics,metabolism Signal Transduction T-Lymphocyte Subsets/cytology,immunology T-Lymphocytes, Helper-Inducer/cytology,immunology Transcription Factors/genetics,metabolism
Chemicals
Bcl6 protein, mouse Cytokines DNA-Binding Proteins Prdm1 protein, mouse Proto-Oncogene Proteins c-bcl-6 RNA, Messenger Transcription Factors Positive Regulatory Domain I-Binding Factor 1
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Johnston Robert J
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), 9420 Athena Circle, La Jolla, CA 92037, USA.
Poholek Amanda C
DiToro Daniel
Yusuf Isharat
Eto Danelle
Barnett Burton
Dent Alexander L
Craft Joe
Crotty Shane
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38 references, click to expand
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1175870
Published
2009-08-21
Epub
2009-00-16
Pages
1006-10
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2766560
Subset
IM
Grants
NIAMS NIH HHS · R37 AR040072 · United States
NIAID NIH HHS · R01 AI063107-01A1 · United States
NIAMS NIH HHS · P30 AR053495 · United States
NIAMS NIH HHS · AR40072 · United States
PHS HHS · R01 072543 · United States
NIAID NIH HHS · R01 AI063107 · United States
NIAID NIH HHS · R01 AI072543-01A1 · United States
NIAMS NIH HHS · AR44076 · United States
NIAID NIH HHS · R01 AI072543 · United States
PHS HHS · R01 063107 · United States
Databases
GEO
GSE16697
Corrections
CommentIn
PMID: 19696339
External Links
PubMed source DOI: 10.1126/science.1175870 PMC Full Text View journal details
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