Rearranged antibody genes in B lymphocytes are subjected to somatic hypermutation mediated by activation-induced cytidine deaminase (AID) in order to increase antibody diversity. Buerstedde et al. used a fluorescent reporter system for somatic hypermutation in a B cell line to test the ability of mouse and human regulatory elements to enhance somatic hypermutation. They found that different immunoglobulin enhancer and enhancer-like elements cooperated to promote somatic hypermutation, which may be important for restricting AID-mediated mutagenesis to appropriate loci.