BCL-6 Represses Genes that Function in Lymphocyte Differentiation, Inflammation, and Cell Cycle Control

• Published in: Immunity (Cambridge, Mass.) Vol. 13; no. 2; pp. 199 - 212
• Main Authors: Shaffer, A.L, Yu, Xin, He, Yunsheng, Boldrick, Jennifer, Chan, Erick P, Staudt, Louis M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2000
• Subjects: Animals; B-Lymphocytes - cytology; B-Lymphocytes - physiology; Bcl-6 protein; Cell Cycle - genetics; Cell Differentiation - genetics; Cells, Cultured; DNA-Binding Proteins - genetics; Gene Expression Regulation; Inflammation - genetics; Mice; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-6; Signal Transduction - genetics; Transcription Factors - genetics; Transcription, Genetic
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)00020-0

BCL-6, a transcriptional repressor frequently translocated in lymphomas, regulates germinal center B cell differentiation and inflammation. DNA microarray screening identified genes repressed by BCL-6, including many lymphocyte activation genes, suggesting that BCL-6 modulates B cell receptor signals. BCL-6 repression of two chemokine genes, MIP-1α and IP-10, may also attenuate inflammatory responses. Blimp-1, another BCL-6 target, is important for plasmacytic differentiation. Since BCL-6 expression is silenced in plasma cells, repression of blimp-1 by BCL-6 may control plasmacytic differentiation. Indeed, inhibition of BCL-6 function initiated changes indicative of plasmacytic differentiation, including decreased expression of c-Myc and increased expression of the cell cycle inhibitor p27kip1. These data suggest that malignant transformation by BCL-6 involves inhibition of differentiation and enhanced proliferation.