Mercuric chloride-, gold sodium thiomalate-, and D-penicillamine-induced antinuclear antibodies in mice.
Inducibility of antinuclear antibodies (ANA) by mercuric chloride (HgCl2) was studied in various strains of mice. High response to the treatment was observed in strains A.SW (H-2s), A.CA (H-2f), A.TH (H-2t2), B10.S (H-2s), DBA/1J (H-2q), and P/J (H-2p); strains A.BY (H-2b), B10.M (H-2f), and C3H/HeSnJ (H-2k) showed a low response, while strains A/WySn (H-2a), A/J (H-2a), A.TL (H-2tl), BALB/cJ (H-2d), C57BL/10SnJ (H-2b), B10.A (H-2a), and PL/J (H-2u) did not produce any detectable ANA. Thus, the H-2a haplotype determines resistance to the treatment regardless of the genetic background; the H-2s determines susceptibility, while the H-2b and H-2f are intermediate haplotypes whose effect depends on the interaction with the background genes. Our results with intra-H-2 recombinant strains indicate that the I region of the H-2 complex is the major genetic factor controlling this response. The function of the I region is to control cellular cooperation in the immune response that finally results in production of antibodies specific for a particular antigen. Therefore, we postulated that the I region controls the antibody response to a nuclear antigen released as a result of HgCl2 toxicity in mice. A genetic study of an A.SW X C57BL/10 cross confirmed this observation, showing that resistance to ANA induction by HgCl2 in this strain combination is determined by interaction of a semidominant H-2-linked gene and one or more unlinked genes. The two drugs tested, gold sodium thiomalate and D-penicillamine, also induced ANA in A.SW mice, while other strains tested resisted this treatment.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006183:H-2 Antigens / Q000235:genetics; D008627:Mercuric Chloride / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010396:Penicillamine / Q000494:pharmacology*; D013045:Species Specificity
D000974:Antibodies, Antinuclear; D006183:H-2 Antigens; D006052:Gold Sodium Thiomalate; D008627:Mercuric Chloride; D010396:Penicillamine