Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice

Abstract

Diffuse large B cell lymphomas (DLBCL) derive from germinal center (GC) B cells and display chromosomal alterations deregulating the expression of BCL6, a transcriptional repressor required for GC formation. To investigate the role of BCL6 in DLBCL pathogenesis, we have engineered mice that express BCL6 constitutively in B cells by mimicking a chromosomal translocation found in human DLBCL. These mice display increased GC formation and perturbed post-GC differentiation characterized by a decreased number of post-isotype switch plasma cells. Subsequently, these mice develop a lympho- proliferative syndrome that culminates with the development of lymphomas displaying features typical of human DLBCL. These results define the oncogenic role of BCL6 in the pathogenesis of DLBCL and provide a faithful mouse model of this common disease