Control of inflammation, cytokine expression, and germinal center formation by BCL-6.
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.
Dent
A L
AL
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shaffer
A L
AL
Yu
X
X
Allman
D
D
Staudt
L M
LM
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D009205:Myocarditis / Q000276:immunology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051560:Proto-Oncogene Proteins c-bcl-6; D017455:Receptors, IgE / Q000235:genetics; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014301:Trinitrobenzenes / Q000276:immunology; D014657:Vasculitis / Q000276:immunology / Q000473:pathology
D016207:Cytokines; D004268:DNA-Binding Proteins; D006241:Haptens; D007136:Immunoglobulins; D007378:Interleukins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D017455:Receptors, IgE; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C020529:TNP-ficoll; D015534:Trans-Activators; D014157:Transcription Factors; D014301:Trinitrobenzenes; C054401:trinitrophenyl keyhole limpet hemocyanin; D015847:Interleukin-4; D005362:Ficoll; D007371:Interferon-gamma; D006433:Hemocyanins