Intrinsic bias and public rearrangements in the human immunoglobulin Vλ light chain repertoire

K. H. Hoi, G. C. Ippolito

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The immunoglobulin lambda (IGL) repertoires from two unrelated human blood samples, three NOD-scid-IL2Rγ null mice engrafted with human hematopoietic stem cells and two pairs of monozygotic twin blood samples were determined by Roche 454 sequencing to generate a total of about 700 000 IGL sequences. We applied bioinformatic analysis to examine IGL repertoires wherein, surprisingly, ≥20% of CDR-L3 peptide sequences were 'public' (shared across individuals); moreover, full-length IGL protein sequences (VJ recombinants) were also present in the public domain. Subtle yet significant differences in CDR-L3 nontemplated nucleotide addition, IGL V-gene family usage, and amino-acid composition distinguished the public CDR-L3 groups from the private groups. These data suggest that public CDR-L3 intervals can arise by intrinsic genetic mechanisms irrespective of different B-cell developmental milieu (human versus humanized mouse). Furthermore, the occurrence of identical public IGL protein sequences indirectly suggest the positive selection (evolutionary, somatic or both) of particular IGL chains independent of the immunoglobulin heavy chain.

Original languageEnglish (US)
Pages (from-to)271-276
Number of pages6
JournalGenes and Immunity
Volume14
Issue number4
DOIs
StatePublished - Jun 2013

Keywords

  • CDR-L3
  • human
  • humanized mice
  • immunoglobulin repertoire
  • lambda light chain
  • next-generation sequencing

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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