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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.Sle1(z) mice were compared to non-nuclear antibody controls. Compared
to two different sets of non-nuclear antibodies, anti-nucleosome antibodies derived
from B6.Sle1(z) 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 approximately
4-fold.