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Dent, AL, Shaffer, AL, Yu, X, Allman, D and Staudt, LM (1997) Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science 276:589-92
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.
Animals; B-Lymphocytes/immunology; Cells, Cultured; Cytokines/biosynthesis; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Ficoll/analogs & derivatives; Ficoll/immunology; Germinal Center/immunology; Hemocyanin/immunology; Immunoglobulins/biosynthesis; Inflammation/immunology; Inflammation/pathology; Interferon-gamma/biosynthesis; Interleukin-4/metabolism; Interleukins/biosynthesis; Interleukins/metabolism; Lymphocyte Activation; Mice; Myocarditis/immunology; Myocarditis/pathology; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology; Proto-Oncogene Proteins c-bcl-6; Receptors, IgE/genetics; STAT6 Transcription Factor; Signal Transduction; Spleen/immunology; T-Lymphocytes/immunology; Th2 Cells/immunology; Trans-Activators/metabolism; Transcription Factors/genetics; Transcription Factors/physiology; Transcription, Genetic; Trinitrobenzenes/immunology; Vasculitis/immunology; Vasculitis/pathology
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