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The Journal of Immunology, 1998, 161: 294-301.
Copyright © 1998 by The American Association of Immunologists

A {lambda} 3' Enhancer Drives Active and Untemplated Somatic Hypermutation of a {lambda}1 Transgene1

Qingzhong Kong*, Lisa Zhao2,*, Sathish Subbaiah3,* and Nancy Maizels4,*,{dagger}

Departments of * Molecular Biophysics and Biochemistry and {dagger} Genetics, Yale University, New Haven, CT 06520

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.




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