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 path ay. 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 lympho-magenesis. Copyright (C) 2002 John Wiley Sons, Ltd.