Somatic variants of murine immunoglobulin λ light chains

Alfred L.M. Bothwell, Michael Paskind, Michael Reth, Thereza Imanishi-kari, Klaus Rajewsky, David Baltimore

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)380-382
Number of pages3
JournalNature
Volume298
Issue number5872
DOIs
StatePublished - 1982
Externally publishedYes

ASJC Scopus subject areas

  • General

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