Murine silver-induced autoimmunity: silver shares induction of antinucleolar antibodies with mercury, but causes less activation of the immune system.
BACKGROUND
Mercury and silver induce antinucleolar autoantibodies (ANoA) targeting the 34-kDa nucleolar protein fibrillarin in susceptible mouse strains. Mercury has the ability to cause a general activation of the immune system, but antigen-specific mechanisms following direct or indirect interaction between mercury and fibrillarin are now believed to play a crucial role in the autoimmune pathogenesis. Our previous studies showed that silver neither induced the systemic immune complex deposits nor the increase of serum immunoglobulins seen after mercury treatment. The main objective of this study was to examine the relation between activation of the immune system and the induction of ANoA.


METHODS
During 4 weeks of subcutaneous silver nitrate injections into mice of the susceptible A.SW and SJL strains and the resistant A.TL strain, the number of T and B cells as well as the expression of cell surface activation and proliferation markers were monitored by flow cytometry. The number of cytoplasmic Ig+ splenocytes was determined by direct immunofluorescence technique on slides, and serum Ig levels as well as anti-ssDNA anti anti-DNP antibodies were determined by ELISA. Serum ANoA were monitored by the indirect immunofluorescence technique.


RESULTS
Silver caused in the susceptible strains a weaker and later activation and proliferation of T and B cells than mercury, and no significant polyclonal B cell activation. In contrast, the ANoA titer was not different from that seen in mercury-treated mice of the same strains. Silver-treated mice of the A.TL strain showed neither activation of the immune system nor ANoA.


CONCLUSIONS
Despite being as effective as mercury inducing ANoA, silver caused only a slight activation of the immune system. This demonstrates that the massive activation of the immune system in mercury treatment is not necessary for the induction of ANoA, and indicates that (auto)antigen-specific mechanisms are likely to play a key role in mercury- and silver-induced murine autoimmunity.
Johansson
U
U
Department of Pathology, Linköping University, Sweden.
Hansson-Georgiadis
H
H
Hultman
P
P
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis / Q000097:blood / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D004277:DNA, Single-Stranded / Q000276:immunology; D004140:Dinitrophenols / Q000276:immunology; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D019084:Fluorescent Antibody Technique, Indirect; D007136:Immunoglobulins / Q000032:analysis / Q000097:blood / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D012835:Silver Nitrate / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000974:Antibodies, Antinuclear; D004277:DNA, Single-Stranded; D004140:Dinitrophenols; D007136:Immunoglobulins; D012835:Silver Nitrate