Somatic mutation in constant regions of mouse lambda 1 light chains.
To study the distribution of somatic mutation, we determined nucleotide sequences of rearranged lambda 1-chain genomic DNA from four hybridomas obtained from C57BL/6 mice that had been immunized with (4-hydroxy-3-nitrophenyl)acetyl-conjugated chicken gamma globulin. In total, 114 nucleotide substitutions were observed, with neither insertion nor deletion. Sixty-one mutations occurred in the variable-joining region genes (V lambda 1-J lambda 1) and 49 in joining-constant (J lambda 1-C lambda 1) introns. Although frequency decreased with distance from the V lambda 1-J lambda 1 coding region, somatic mutations occurred in the entire J lambda 1-C lambda 1 intron and even in the C lambda 1 region. We found four nucleotide substitutions in C lambda 1 genes, all of which were replacement mutations. Therefore, the mechanism responsible for somatic mutation is operative into the C lambda 1 exons. Nucleotide sequences of rearranged but inactive lambda 2-chain genes from two hybridomas were also examined and compared with those of lambda 1-chain genes. The clustering of replacement mutations in complementarity-determining regions in the inactive lambda 2-chain genes similar to the active lambda 1-chain genes suggested a mechanism that induces somatic mutation preferentially in this region even in the absence of antigenic selection.
Motoyama
N
N
Department of Molecular Biology, Nagoya City University School of Medicine, Japan.
Okada
H
H
Azuma
T
T
D000818:Animals; D000916:Antibody Diversity; D001483:Base Sequence; D003001:Cloning, Molecular; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction
D007127:Immunoglobulin Constant Regions; D007146:Immunoglobulin lambda-Chains; D009841:Oligonucleotides