Abstract
The gene encoding the BCL-6 transcriptional repressor is frequently translocated and mutated in diffuse large cell lymphoma. Mice with a disrupted BCL-6 gene developed myocarditis and pulmonary vasculitis, had no germinal centers, and had increased expression of T helper cell type 2 cytokines. The BCL-6 DNA recognition motif resembled sites bound by the STAT (signal transducers and activators of transcription) transcription factors, which mediate cytokine signaling. BCL-6 could repress interleukin-4 (IL-4)-induced transcription when bound to a site recognized by the IL-4-responsive transcription factor Stat6. Thus, dysregulation of STAT-responsive genes may underlie the inflammatory disease in BCL-6-deficient mice and participate in lymphoid malignancies.
MeSH terms
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Animals
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B-Lymphocytes / immunology
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Cells, Cultured
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Cytokines / biosynthesis*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Ficoll / analogs & derivatives
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Ficoll / immunology
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Germinal Center / immunology*
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Haptens
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Hemocyanins / immunology
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Immunoglobulins / biosynthesis
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Inflammation / immunology*
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Inflammation / pathology
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Interferon-gamma / biosynthesis
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Interleukin-4 / metabolism
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Interleukins / biosynthesis
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Interleukins / metabolism
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Lymphocyte Activation
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Mice
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Myocarditis / immunology
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Myocarditis / pathology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-bcl-6
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Receptors, IgE / genetics
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STAT6 Transcription Factor
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Signal Transduction
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Spleen / immunology
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T-Lymphocytes / immunology
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Th2 Cells / immunology
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Trans-Activators / metabolism
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transcription, Genetic
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Trinitrobenzenes / immunology
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Vasculitis / immunology
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Vasculitis / pathology
Substances
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Cytokines
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DNA-Binding Proteins
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Haptens
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Immunoglobulins
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Interleukins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-6
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Receptors, IgE
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STAT6 Transcription Factor
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Stat6 protein, mouse
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TNP-ficoll
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Trans-Activators
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Transcription Factors
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Trinitrobenzenes
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trinitrophenyl keyhole limpet hemocyanin
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Interleukin-4
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Ficoll
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Interferon-gamma
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Hemocyanins