Premium
Antigen specificity of anti‐nuclear antibodies complexed to nucleosomes determines glomerular basement membrane binding in vivo
Author(s) -
Van Bruggen Mieke C. J.,
Walgreen Birgitte,
Rijke Truus P. M.,
Tamboer Wim,
Kramers Kees,
Smeenk Ruud J. T.,
Monestier Marc,
Fournie Gilbert J.,
Berden Jo H. M.
Publication year - 1997
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830270636
Subject(s) - biology , microbiology and biotechnology , antibody , histone , nucleosome , immune complex , autoantibody , chromatosome , in vivo , dna , biochemistry , immunology , genetics
Abstract Monoclonal anti‐nuclear antibodies which are complexed to nucleosomes are able to bind to the glomerular basement membrane (GBM) in vivo , whereas purified antibodies do not bind. The positively charged histone moieties in the nucleosome are responsible for the binding to anionic determinants in the GBM. We tested the hypothesis that the specificity of the autoantibodies complexed to the nucleosome influences the glomerular binding of the antibody‐nucleosome complex. We induced the formation of these immune complexes in vivo , by intraperitoneal inoculation of hybridomas producing monoclonal anti‐nuclear 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 mice inoculated with these hybridomas, nucleosome/autoantibody complexes were detected in comparable amounts. Immunofluorescence of kidney sections revealed that about 60% of the mice inoculated with anti‐nucleosome or anti‐dsDNA hybridomas had immunoglobulin deposits in the GBM, whereas only 15% of the mice with anti‐histone hybridomas showed these deposits ( p ≦ 0.04). In the Matrigel ® ‐ELISA (used as a GBM surrogate) ascites from anti‐nucleosome or anti‐DNA hybridomas displayed significantly higher titers ( p ≦ 0.002) than ascites from anti‐histone hybridomas. In conclusion, nucleosome/immunoglobulin complexes comprising anti‐nucleosome or anti‐dsDNA auto‐antibodies do bind more frequently to the GBM in vivo than nucleosome/immunoglobulin complexes containing anti‐histone antibodies. It therefore appears that the specificity of the antibody bound to the nucleosome is a critical determinant for the nephritogenic potential of the nucleosome‐autoantibody complex.