The Endless Complexity of Lymphocyte Differentiation and Lymphomagenesis: IRF-4 Downregulates BCL6 Expression

The BCL6 gene is a key factor necessary for formation of germinal centers and is implicated in pathogenesis of diffuse large B cell lymphoma (DLBCL). In this issue of Cancer Cell, Saito and colleagues explore regulation of BCL6 gene expression by CD40-NF-κB signaling pathway and show that the IRF4 transcriptional factor, induced by the NF-κB canonical pathway, directly downregulates BCL6 expression. The authors further demonstrate that this negative regulatory mechanism may be disturbed in DLBCLs harboring BCL6 gene translocations or mutations. These finding suggest that IRF4 may function as a key regulator of germinal center reaction and a guardian of lymphomagenesis.