Murine susceptibility to mercury. I. Autoantibody profiles and systemic immune deposits in inbred, congenic, and intra-H-2 recombinant strains.
Inbred, congenic, and intra-H-2-recombinant mouse strains were given subcutaneous injections of either 1.6 mg HgCl2/kg body wt or 0.1 ml NaCl thrice weekly for 5-6 weeks. Mercury-treated mice from strains carrying the H-2s haplotype developed antinucleolar antibodies (ANoA), which targeted the 34-kDa nucleolar protein fibrillarin, and in some instances also nucleolar proteins of 60-70 and 10-15 kDa, the latter corresponding to histones. Strains with H-2b and H-2d haplotypes were resistant to induction of ANoA. The susceptibility to development of AnoA/antifibrillarin antibodies (AFA) was mapped to the H-2A-region using intra-H-2-recombinant strains. We were not able to confirm earlier reports that expression of H-2E genes dampens the development of ANoA. Mercury treatment caused a substantial increase in the titer of antichromatin (ACA) and/or antihistone (AHA) antibodies in a fraction of SJL/J, A.SW, A.TH, B10.S, and B10.HTT mice (H-2s), and in A/J (H-2k) mice, whereas mice from the C57BL/6J and C57BL/10J (H-2b), and the DBA and BALB/c (H-2d) strains were low or nonresponders. The development of AHA and ACA could not be linked to the H-2 complex. A significant, substantial increase of granular mesangial and systemic vessel wall IgG deposits occurred in mice with serum ANoA/AFA. However, the B10.S(9R) and B10.HTT strains, which express the H-2E genes, developed only an intermediately increased titer of mesangial IgG deposits. Systemic vessel wall IgG deposits occurred in only 60-80% of the B10.S(9R) mice and in none of the B10.HTT mice. This contrasted with the high titer of mesangial IgG deposits and uniform development of systemic vessel wall IgG deposits observed in B10.S mice not expressing H-2E. Mice with mesangial IgG deposits showed a mild glomerulonephritis. There was no systemic vasculitis. The susceptibility to development of ANoA, AHA, ACA, and systemic, granular IgG deposits in the B10.S strain was influenced by the sex, since males showed less uniform development of these immunopathologic features than females.
Hultman
P
P
Department of Pathology I, Linköping University, Sweden.
Bell
L J
LJ
Eneström
S
S
Pollard
K M
KM
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D001323:Autoantibodies / Q000096:biosynthesis; D002843:Chromatin / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006183:H-2 Antigens / Q000276:immunology*; D006657:Histones / Q000276:immunology; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D007668:Kidney / Q000276:immunology; D008297:Male; D008628:Mercury / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000276:immunology; D013154:Spleen / Q000276:immunology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D002843:Chromatin; D006183:H-2 Antigens; D006657:Histones; D007074:Immunoglobulin G; D008628:Mercury