Studies of the murine λ1 light chains produced by myeloma cells provided the first evidence for somatic point mutation of germ-line variable (V) region genes. An examination of the variable regions of 19 λ1 chains revealed seven which differed from a common sequence by one to three amino acid substitutions1. Subsequently, one of these presumed somatic variants of the single λ1 V gene was characterized by DNA sequence analysis of the rearranged functional gene2. The predicted DNA sequence alteration was observed and no silent mutation was evident. These studies of λ chain variants suggested that the hypervariable, complementarity-determining regions (CDRs) ht be a preferred site of somatic mutation because all seven characterized variants contained substitutions only in these regions. By contrast, comparisons of closely related κ chain variable region amino acid sequences, and more recently Vκ and VH genes8-12, have suggested that somatic mutation probably occurs in codons for both framework and CDR residues. To examine this apparent discrepancy between the sites of somatic mutation in λ and κ genes, we have determined the nucleotide sequence of two λ 1 gene from hybridomas and a λ 2 gene from a myeloma. These sequences demonstrate that somatic mutation in λ genes can occur in both the framework and CDR residues.
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