A λ 3' enhancer drives active and untemplated somatic hypermutation of a λ₁ 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 A light chain gene. We have studied somatic hypermutation of a rearranged λ₁ transgene under the control of either a λ_2-4 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.