Targeting and selection of mutations in human Vλ rearrangements

Nancy L. Monson, Thomas Dörner, Peter E. Lipsky

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The impact of somatic hypermutation on the lambda light chain repertoire of individual IgM+ peripheral B cells in the absence (nonproductive rearrangements) and presence (productive rearrangements) of selective influences was analyzed. In the 27 mutated nonproductive VλJλ rearrangements obtained from individual peripheral B cells, a significantly greater mutational frequency was observed in the complementarity-determining region (CDR) in comparison to the framework region (FR), whereas the mutational frequencies in both the CDR and FR of the 100 mutated productive VλJλ rearrangements were significantly greater. R mutations were introduced comparably in CDR and FR of nonproductive VλJλ rearrangements, but were significantly decreased in FR of productive VλJλ rearrangements. The majority of codons defined as hot spots for R mutations were within CDR in both the nonproductive and productive VλJλ rearrangements. Targeting of mutations to RGYW/WRCY motifs was observed such that 38% of all mutations in the nonproductive VλJλ rearrangements were within RGYW/WRCY motifs. Mutations in RGYW/WRCY motifs were positively selected and accounted for > 50% of all mutations in the mutated productive VλJλ rearrangements. These data indicate that targeting of the mutational machinery and selection of mutations in these targeted motifs play major roles in influencing nucleotide changes in VλJλ rearrangements.

Original languageEnglish (US)
Pages (from-to)1597-1605
Number of pages9
JournalEuropean Journal of Immunology
Volume30
Issue number6
DOIs
StatePublished - Jun 21 2000

Keywords

  • Antibody
  • B lymphocyte
  • Generation of diversity, and evolution
  • Human

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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