Genetic susceptibility to silver-induced anti-fibrillarin autoantibodies in mice

Clin Immunol Immunopathol. 1995 Dec;77(3):291-7. doi: 10.1006/clin.1995.1155.


Similar to mercuric chloride, silver nitrate has recently been shown to induce IgG autoantibodies targeting the nucleolar 34-kDa protein fibrillarin i SJL (H-2s) mice. In the present study we show that the autoimmunogenic effect of silver is dependent on intact T-cell function since SJL/N mice homozygous for the nude mutation (athymic), in contrast to the functionally T-cell-intact SJL/N-nu/+ littermates, did not develop anti-nucleolar/anti-fibrillarin autoantibodies (ANoA/AFA). The genetic susceptibility for silver-induced AFA was localized to the H-2A locus using congenic and intra-H-2-recombinant strains. However, background (non-H-2) genetic factors substantially influenced both the response rate and the titer of ANoA/AFA attained. Strains bearing H-2As on the SJL and A backgrounds (SJL, A.SW, A.TH) showed 100% response rate and high ANoA titers (3750 +/- 246, mean reciprocal titer +/- SEM), whereas H-2As mice on the B10 background (B10.S) showed 60% response rate and significantly lower ANoA titers (1170 +/- 305) in the responding mice. Expression of H-2E [B10.S(9R) mice] further reduced the response rate (22%) and the ANoA titer (640 +/- 0). A suppressive effect on the B10 background has previously been observed in mercury treatment, but the effect was stronger in silver-treated mice. Two major differences were noted between silver- and mercury-induced murine autoimmunity. First, silver-treated mice did not show elevated titers of other autoantibody specificities, specifically not of antichromatin and anti-histone antibodies, which develop in mercury-treated SJL mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / immunology*
  • Autoimmunity / drug effects*
  • Autoimmunity / genetics*
  • Blood Vessels / immunology
  • Cell Nucleolus / immunology
  • Chromatin / immunology
  • Chromosomal Proteins, Non-Histone / immunology*
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Glomerular Mesangium / immunology
  • Histones / immunology
  • Immunoblotting
  • Mice
  • Mice, Inbred Strains
  • Silver Nitrate / toxicity*


  • Antibodies, Antinuclear
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Histones
  • fibrillarin
  • Silver Nitrate