The proto-oncogene BCL-6 in normal and malignant B cell development.
BCL-6 is an important regulator of the immune system. It is required for GC formation and T cell dependent antibody responses. Mice deficient in BCL-6 fail to form GC and mount reduced levels of T cell-dependent antibody responses. BCL-6 (-/-) mice, in addition, develop a massive inflammatory response in many organs characterized by eosinophilic infiltration and hyper-IgE production, a typical Th2 hyperimmune response. This suggests a negative role of BCL-6 in Th2 pathway. The BCL-6 gene encodes a POZ/zinc finger transcription repressor highly expressed in GC B cells, but not in pre-GC B cells or in more differentiated memory or plasma cells. By functioning as a potent transcriptional repressor of various target genes, BCL-6 modulates IL-4, BCR, and CD40L signals for normal B cell development. In B cell lymphomas, structural alterations of the BCL-6 promoter region, including chromosome translocation and somatic hypermutation, represent the most frequent genetic lesions associated with non-Hodgkin lymphoma, especially of diffuse large cell lymphoma, a malignancy often derived from germinal centre (GC) B cells. This suggests that deregulated expression of BCL-6 may contribute to lymphomagenesis.
Niu
Huifeng
H
Institute of Cancer Genetics, University of Columbia, New York, NY 10032, USA.
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D023201:CD40 Ligand