Abstract
The transcription factor Bcl-6 orchestrates germinal center (GC) reactions through its actions in B cells and T cells and regulates inflammatory signaling in macrophages. Here we found that genetic replacement with mutated Bcl6 encoding Bcl-6 that cannot bind corepressors to its BTB domain resulted in disruption of the formation of GCs and affinity maturation of immunoglobulins due to a defect in the proliferation and survival of B cells. In contrast, loss of function of the BTB domain had no effect on the differentiation and function of follicular helper T cells or that of other helper T cell subsets. Bcl6-null mice had a lethal inflammatory phenotype, whereas mice with a mutant BTB domain had normal healthy lives with no inflammation. The repression of inflammatory responses by Bcl-6 in macrophages was accordingly independent of the repressor function of the BTB domain. Bcl-6 thus mediates its actions through lineage-specific biochemical functions.
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 Affinity / immunology
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B-Lymphocytes / immunology
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Cell Lineage / genetics*
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Cell Lineage / immunology*
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Cell Survival / genetics
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Cell Survival / immunology
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Chemokines / immunology
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Chemokines / metabolism
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Female
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Germinal Center / cytology
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Germinal Center / immunology
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Germinal Center / metabolism
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Immunoglobulins / immunology
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Immunoglobulins / metabolism
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Inflammation / genetics*
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Inflammation / immunology*
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Lymphocyte Activation / immunology
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Mice, Knockout
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Phenotype
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Proto-Oncogene Proteins c-bcl-6 / genetics*
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Proto-Oncogene Proteins c-bcl-6 / immunology*
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Proto-Oncogene Proteins c-bcl-6 / 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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T-Lymphocytes, Helper-Inducer / metabolism
Substances
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Chemokines
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Immunoglobulins
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Proto-Oncogene Proteins c-bcl-6