The proto‐oncogene BCL‐6 in normal and malignant B cell development

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Abstract
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. Copyright © 2002 John Wiley & Sons, Ltd.