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 language | English (US) |
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Pages (from-to) | 2671-2681 |
Number of pages | 11 |
Journal | Molecular Immunology |
Volume | 46 |
Issue number | 13 |
DOIs | |
State | Published - Aug 2009 |
Keywords
- Autoantibodies
- Autoimmunity
- B-cells
- Genetics
- Immunoglobulin repertoire
ASJC Scopus subject areas
- Immunology
- Molecular Biology