title: Mercuric chloride-, gold sodium thiomalate-, and D-penicillamine-induced antinuclear antibodies in mice.
abstract: 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.
mesh_terms: 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
chemical_list: D000974:Antibodies, Antinuclear; D006183:H-2 Antigens; D006052:Gold Sodium Thiomalate; D008627:Mercuric Chloride; D010396:Penicillamine