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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody Formation
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B-Lymphocytes / immunology
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Cell Differentiation
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Cell Lineage
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Cytokines / immunology
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Cytokines / metabolism
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Germinal Center / cytology
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Germinal Center / immunology*
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Immunoglobulins / biosynthesis
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Interleukin-6 / immunology
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Interleukin-6 / metabolism
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Interleukins / immunology
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Interleukins / metabolism
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Lymphocyte Activation
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Mutation
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Proto-Oncogene Proteins c-bcl-6
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Bcl6 protein, mouse
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Cytokines
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DNA-Binding Proteins
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Immunoglobulins
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Interleukin-6
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Interleukins
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Proto-Oncogene Proteins c-bcl-6
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RNA, Messenger
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Transcription Factors
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interleukin-21