ANTIGEN-SPECIFICITY OF ANTINUCLEAR ANTIBODIES COMPLEXED TO NUCLEOSOMES DETERMINES GLOMERULAR-BASEMENT-MEMBRANE BINDING IN-VIVO

Monoclonal anti-nuclear antibodies which are complexed to nucleosomes are able to bind to the glomerular basement membrane (GEM) in vivo, wh ereas purified antibodies do not bind. The positively charged histone moieties in the nucleosome are responsible for the binding to anionic determinants in the GEM. We tested the hypothesis that the specificity of the autoantibodies complexed to the nucleosome influences the glom erular binding of the antibody-nucleosome complex. We induced the form ation of these immune complexes in vivo, by intraperitoneal inoculatio n of hybridomas producing monoclonal antinuclear antibodies (four anti -histone, three anti-double stranded (ds)DNA and three anti-nucleosome antibodies) into nude BALB/c mice. In ascites and plasma from the mic e inoculated with these hybridomas, nucleosome/autoantibody complexes were detected in comparable amounts. Immunofluorescence of kidney sect ions revealed that about 60% of the mice inoculated with anti-nucleoso me or anti-dsDNA hybridomas had immunoglobulin deposits in the GEM, wh ereas only 15 % of the mice with anti-histone hybridomas showed these deposits (p less than or equal to 0.04). In the Matrigel(R)-ELISA (use d as a GEM surrogate) ascites from anti-nucleosome or anti-DNA hybrido mas displayed significantly higher titers (p less than or equal to 0.0 02) than ascites from anti-histone hybridomas. In conclusion, nucleoso me/immunoglobulin complexes comprising anti-nucleosome or anti-dsDNA a uto-antibodies do bind more frequently to the GEM in vivo than nucleos ome/immunoglobulin complexes containing anti-histone antibodies. It th erefore appears that the specificity of the antibody bound to the nucl eosome is a critical determinant for the nephritogenic potential of th e nucleosome-autoantibody complex.