A Signaling Pathway Mediating Downregulation of BCL6 in Germinal Center B Cells Is Blocked by BCL6 Gene Alterations in B Cell Lymphoma
2007; Cell Press; Volume: 12; Issue: 3 Linguagem: Inglês
10.1016/j.ccr.2007.08.011
ISSN1878-3686
AutoresMasumichi Saito, Jie Gao, Katia Basso, Yukiko Kitagawa, Paula Marincola Smith, Govind Bhagat, Alessandra B. Pernis, Laura Pasqualucci, Riccardo Dalla‐Favera,
Tópico(s)Immune Cell Function and Interaction
ResumoSummary The BCL6 proto-oncogene encodes a transcriptional repressor necessary for the development of germinal centers (GCs) and directly implicated in lymphomagenesis. Post-GC development of B cells requires BCL6 downregulation, while its constitutive expression caused by chromosomal translocations leads to diffuse large B cell lymphoma (DLBCL). Herein we identify a signaling pathway that downregulates BCL6 expression in normal GC B cells and is blocked in a subset of DLBCL due to alterations in the BCL6 gene. Activation of the CD40 receptor leads to NF-κB-mediated induction of the IRF4 transcription factor, which, in turn, represses BCL6 expression by binding to its promoter region. A subset of DLBCL displays chromosomal translocations or mutations that disrupt the IRF4-responsive region in the BCL6 promoter and block its downregulation by CD40 signaling.
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