MURINE GENOTYPE INFLUENCES THE SPECIFICITY, MAGNITUDE AND PERSISTENCEOF MURINE MERCURY-INDUCED AUTOIMMUNITY

Genetic factors are major contributors in determining the susceptibili ty to systemic autoimmune diseases. We studied the influence of genoty pe on systemic autoimmunity by treating female mice of the H-2(s) stra ins SJL/N, SJL/J, A.SW, and B10.S with mercuric chloride (HgCl2) for 1 0 weeks and then following autoantibody and tissue immune deposits dur ing the subsequent 12 months. All strains developed antinucleolar anti bodies (ANoA) of the IgG class which reacted in immunoblotting with a 34-kDa nucleolar protein identified as fibrillarin. The titre of ANoA attained after 10 weeks' treatment varied from 1:1,280 to 1:20,480 in the order: A.SW>SJL much greater than B10.S. Following cessation of Hg Cl2 treatment ANoA and antifibrillarin antibodies (AFA) persisted for up to 12 months, although some B10.S mice showed pronounced reduction not only of their autoantibody titres, but also systemic immune deposi ts when compared to other H-2(s) strains. A second set of autoantibodi es targeted chromatin and in some mice specifically histones, and were distinguished from the ANoA by a rapid decline after treatment and a susceptibility linked to the non-H-2 genes of the SJL. Tissue levels o f mercury remained elevated above untreated controls throughout the st udy period, suggesting that the mercury detected in lymphoid tissues m ay provide stimulation of lymphoid cells specific for fibrillarin for a considerable period after exposure has ceased. We conclude that H-2 as well as non-H-2 genetic factors distinctly influence not only the s usceptibility to induction of autoimmunity, but also the specificity a nd magnitude of the response. (C) 1996 Academic Press Limited