The 5' boundary of somatic hypermutation in a V kappa gene is in the leader intron.

The maturation of the immune response involves the hypermutation of antibody genes and the selection of B cells expressing receptors with improved antigen binding properties. Somatic hypermutation of antibody genes is targeted to a small region approximately 1 kb surrounding the rearranged V gene. The precise definition of the 5' limit is not yet clear since the data base of somatic mutations upstream of the V region is very restricted. The available data suggest that it lies close to the promoter region and this has been used to implicate transcription in the mechanism leading to hypermutation. Here we present an extensive analysis of mutations in the 5' region of a single kappa light chain gene. A large data base from highly mutated sequences was obtained from anti-oxazolone hybridomas expressing the V kappa Ox1-J kappa 5 light chain and from polymerase chain reaction-derived clones from splenic and Peyer's patches of transgenic mice expressing the same V kappa Ox1-J kappa 5 gene combination. Although mutations were found in the 5'-flanking segment, the rate of mutation in the V-J segment was about 20-fold higher. A sharp decline between those two mutation rates is evident but the boundary was found in the leader intron of the V kappa Ox1 gene, about 150 bases downstream of the initiation of transcription site.