We uncovered a synergistic interplay whereby heterozygous loss of Crebbp and Kmt2d promotes the preneoplastic expansion of abnormal GCs (the target structure of FL and DLBCL development) by perturbing a unique set of enhancers that are distinct from those affected by either mutation alone and are involved in the regulation of the B:T cell immune synapse and in memory B cell identity. This evidence concerns the gene CREBBP and diffuse large B-cell lymphoma.