Comparison of somatic mutation frequency among immunoglobulin genes.
We analyzed the frequency of somatic mutation in immunoglobulin genes from hybridomas that secrete anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) monoclonal antibodies. A high frequency of mutation (3.3-4.4%) was observed in both the rearranged VH186.2 and V lambda 1 genes, indicating that somatic mutation occurs with similar frequency in these genes in spite of the absence of an intron enhancer in lambda 1 chain genes. In contrast to the high frequency in J-C introns, only two nucleotide substitutions occurred at positions -462 and -555 in the 5' noncoding region in one of the lambda 1-chain genes and in none of the other three so far studied. Since a similar low frequency of somatic mutation was observed in the 5' noncoding region of inactive lambda 2-chain genes rendered inactive because of incorrect rearrangement, this region may not be a target or alternatively, may be protected from the mutator system. We observed a low frequency of nucleotide substitution in unrearranged V lambda 1 genes (approximately 1/15 that of rearranged genes). Together with previous results (Azuma T., N. Motoyama, L. Fields, and D. Loh, 1993. Int. Immunol. 5:121), these findings suggest that the 5' noncoding region, which contains the promoter element, provides a signal for the somatic mutator system and that rearrangement, which brings the promoter into close proximity to the enhancer element, should increase mutation efficiency.
Motoyama
N
N
Department of Molecular Biology, Nagoya City University School of Medicine, Japan.
Miwa
T
T
Suzuki
Y
Y
Okada
H
H
Azuma
T
T
D000818:Animals; D001483:Base Sequence; D004247:DNA; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006825:Hybridomas; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid
D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D004247:DNA