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.
Kong
Q
Q
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Zhao
L
L
Subbaiah
S
S
Maizels
N
N
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D005785:Gene Conversion / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000276:immunology*; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism; D013698:Templates, Genetic; D019076:Transgenes / Q000276:immunology*
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains