BCL6 controls the expression of the B7-1/CD80 costimulatory receptor in germinal center B cells.
The BCL6 proto-oncogene encodes a transcriptional repressor required for the development of germinal centers (GCs) and implicated in the pathogenesis of GC-derived B cell lymphoma. Understanding the precise role of BCL6 in normal GC formation and in lymphomagenesis depends on the identification of genes that are direct targets of its transcriptional repression. Here we report that BCL6 directly controls the expression of B7-1/CD80, a costimulatory receptor involved in B-T cell interactions critical for the development of T cell-mediated antibody responses. Upon CD40 signaling, transcription of the CD80 gene is induced by the nuclear factor (NF)-kappaB transcription factor. Our results show that BCL6 prevents CD40-induced expression of CD80 by binding its promoter region in vivo and suppressing its transcriptional activation by NF-kappaB. Consistent with a physiologic role for BCL6 in suppressing CD80, the expression of these two genes is mutually exclusive in B cells, and BCL6-defective mice show increased expression of CD80 in B cells. The results suggest that BCL6 may directly control the ability of B cell to interact with T cells during normal GC development. In addition, these findings imply that T-B cell interactions may be disrupted in B cell lymphoma expressing deregulated BCL6 genes.
Niu
Huifeng
H
Institute for Cancer Genetics, Columbia University, 1150 St. Nicholas Ave., New York, NY 10032, USA.
Cattoretti
Giorgio
G
Dalla-Favera
Riccardo
R
D015703:Antigens, CD / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics*; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D005822:Genetic Vectors; D018095:Germ-Line Mutation; D006801:Humans; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D051560:Proto-Oncogene Proteins c-bcl-6; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000276:immunology*; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D015703:Antigens, CD; D018122:B7-1 Antigen; 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