A λ 3′ Enhancer Drives Active and Untemplated Somatic Hypermutation of a λ1 Transgene

Abstract

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 λ light chain gene. We have studied somatic hypermutation of a rearranged λ1 transgene under the control of either a λ2-4 or κ 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 λ 3′ enhancer can drive active hypermutation of a λ1 transgene in Peyer’s patch cells. The λ1 transgene under analysis carried two marked Vλ2 genes immediately upstream that could serve as sequence donors in possible gene conversion events. There was no evidence of sequence transfer to the hypermutated λ1 gene, suggesting that gene conversion is not a major mechanism for somatic hypermutation in mice.