Molecular hallmarks of anti-chromatin antibodies associated with the lupus susceptibility locus, Sle1

Zhiyan Liang, Sooghee Chang, Min So Youn, Chandra Mohan

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Anti-nuclear antibodies constitute the hallmark of lupus. The NZM2410-derived Sle1 lupus susceptibility interval on murine chromosome 1 breaches tolerance, leading to the emergence of anti-nuclear autoantibodies targeting nucleosomes. However, little is known about the molecular structure of the anti-nucleosome autoantibodies from this genetically simplified mouse model of lupus. In this study, the immunoglobulin heavy chain and light chain sequences of 50 anti-nuclear monoclonal antibodies derived from five B6.Sle1z mice were compared to non-nuclear antibody controls. Compared to two different sets of non-nuclear antibodies, anti-nucleosome antibodies derived from B6.Sle1z congenic mice exhibited a high degree of clonal expansion and three distinct sequence motifs in their heavy chains - cationic CDR3 stretches, non-anionic CDR2 regions, and an increased frequency of aspartate residues at H50, which together increased the likelihood of an antibody being chromatin-reactive by ∼4-fold.

Original languageEnglish (US)
Pages (from-to)2671-2681
Number of pages11
JournalMolecular Immunology
Volume46
Issue number13
DOIs
StatePublished - Aug 1 2009

Keywords

  • Autoantibodies
  • Autoimmunity
  • B-cells
  • Genetics
  • Immunoglobulin repertoire

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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