Anti-fibrillarin autoantibodies in mercury-treated mice.
Using indirect immunofluorescence (IF) with HEp-2 cells as a substrate serially bled SJL mice were found to gradually develop a high titre of anti-nucleolar antibodies (ANuA) after 3-5 weeks of s.c. injections of 1.6 mg HgCl2/kg body weight every third day. The ANuA showed a clumpy nucleolar pattern of localization and were composed of all IgG subclasses, but contained, in comparison with the antinuclear antibodies (ANA) in MRL-lpr/lpr mice, significantly lower titres of IgG2a and only traces of IgG3. Immunoblotting analysis using purified mouse liver nucleoli revealed that the sera with ANuA identified the same 34-kD nucleolar protein which was targeted by a human scleroderma serum containing autoantibodies monospecific for fibrillarin. In addition, a fraction of the mercury-treated SJL mice developed serum antibodies reacting with 10-15 and 60-70 kD nucleolar proteins in immunoblotting. The presence of serum autoantibodies reacting with the 10-15 kD proteins correlated with significantly increased titres of anti-histone antibodies of the IgG class in ELISA. Some mercury-treated SJL mice also developed a significantly increased titre of anti-histone antibodies of the IgM class. B10.S mice treated with mercuric chloride consistently developed ANuA, which also targeted a 34-kD nucleolar protein. Since anti-fibrillarin antibodies are specific markers of scleroderma, the present animal model may be valuable for studies of the immunological aberrations which are likely to induce this autoimmune response.
Hultman
P
P
Department of Pathology I, Linköping University, Sweden.
Eneström
S
S
Pollard
K M
KM
Tan
E M
EM
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood*; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000032:analysis; D008627:Mercuric Chloride; D051379:Mice; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000276:immunology
D000974:Antibodies, Antinuclear; D002868:Chromosomal Proteins, Non-Histone; D007074:Immunoglobulin G; C047458:fibrillarin; D008627:Mercuric Chloride