Starting with the founder BCL2 translocation common to the pathogenesis of most FL and GCB-DLBCL, we will focus on how genetically engineered mice (GEM) of (epi)genetic alterations shed new lights on the link between B ‘cell-intrinsic’ lesions and their cell-extrinsic functions to drive lymphoma development by promoting the remodeling of an aberrant immune niche and contributing to immune surveillance mechanisms. The gene discussed is BCL2; the disease is diffuse large B-cell lymphoma.