title: Induction of anti-polycation antibodies in H-2s mice by immunization with nuclear antigens.
abstract: Following administration of certain chemicals (heavy metals or lupus-inducing drugs), H-2s mice produce autoantibodies reacting with various nuclear antigens such as fibrillarin in the nucleolus and histones in chromatin. In the present study, we have immunized A.SW (H-2s) mice and their congenic counterparts A.BY (H-2b) mice with bovine thymus nuclei in Freund's adjuvant. As was previously observed with lupus-prone mice, such active immunization did not elicit antinuclear antibodies in any of the experimental groups. Surprisingly, the A.SW immunized with nuclei in adjuvant developed high titers of IgG antibodies that reacted exclusively with synthetic polycations. We obtained several monoclonal IgG antibodies from these mice and verified that these polycation-reactive antibodies were not directed against a specific nuclear antigen. The genetic analysis of the monoclonal antibodies further confirmed their clonal diversity. The mechanisms leading to the appearance of antibodies reactive with highly basic molecules in A.SW mice may be related to their predisposition to produce autoantibodies to cationic nuclear antigens (fibrillarin, histones) during chemically-induced autoimmunity.
authors.affiliation: Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA. marcm@astro.ocis.temple.edu
authors.forename: M
authors.initials: M
authors.lastname: Monestier
authors.forename: C
authors.initials: C
authors.lastname: Stemmer
authors.forename: G L
authors.initials: GL
authors.lastname: Ong
authors.forename: S
authors.initials: S
authors.lastname: Muller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D001483:Base Sequence; D002412:Cations / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D007106:Immune Sera / Q000096:biosynthesis; D007114:Immunization; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000008:administration & dosage / Q000276:immunology*; D011073:Polyamines / Q000276:immunology*; D000071228:Polyelectrolytes
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D001324:Autoantigens; D002412:Cations; D006183:H-2 Antigens; D007106:Immune Sera; D007135:Immunoglobulin Variable Region; D009687:Nuclear Proteins; D011073:Polyamines; D000071228:Polyelectrolytes