Understanding lupus pathology in FcγRIIB-/-yaa mice: autoantibodies and autoantigens (P4008)

Abstract FcγRIIB knock-out mice in B6 background develop a lupus like autoimmune disease. With the addition of the yaa (Y-chromosome autoimmune accelerator) gene, pathogenecity in these male mice is significantly enhanced and autoantibodies switch from nuclear to nucleolar specificity. High titer of λ-light chains immunoglobulin, and anti-RNA antibodies were found in R2-/-yaa serum. Also, R2-/-yaa serum selectively bound 5 major nuclear proteins compared to R2-/- serum. To characterize the autoantibodies produced by R2-/-yaa mice and the nucleolar antigens that react with these antibodies, we have produced hybridomas. Hybridoma H526 produced anti-nucleolar IgG2c-λ antibodies. The antibody binds RNA, a synthetic polyribonucleotide poly (GC)20 and a RNA-associated nucleolar protein, nucleolin. R2-/-yaa serum also found to cross-react with poly (GC)20, nucleolin and also with poly ADP-ribose (PAR). Simultaneous presence of nucleolin and PAR autoantibodies has been found to be associated with lupus. Further characterization of nucleolin modification and lupus development is in progress.