A lambda 3' enhancer drives active and untemplated somatic hypermutation of a lambda 1 transgene.

Somatic hypermutation is a highly regulated process that targets mutations to the rearranged Ig genes. Little is known about the cis-elements required for somatic hypermutation of the lambda light chain gene. We have studied somatic hypermutation of a rearranged lambda 1 transgene under the control of either a lambda 2-4 or kappa 3' enhancer. The mutations in the transgenes were analyzed by sequencing DNA amplified from hypermutating Peyer's patch B cells. The results indicate that the lambda 3' enhancer can drive active hypermutation of a lambda 1 transgene in Peyer's patch cells. The lambda 1 transgene under analysis carried two marked V lambda 2 genes immediately upstream that could serve as sequence donors in possible gene conversion events. There was no evidence of sequence transfer to the hypermutated lambda 1 gene, suggesting that gene conversion is not a major mechanism for somatic hypermutation in mice.