title: Failed self-tolerance and autoimmunity in IgG anti-DNA transgenic mice.
abstract: Transgenic mice were generated that express both the H and L chain genes derived from a hybridoma secreting an IgG2a mAb specific for ds- and ssDNA. This hybridoma is derived from a lupus mouse and can accelerate nephritis in young NZB x NZW F1 female mice and induce clinical nephritis in BALB/c mice. Some transgenic B cells did not exhibit allelic exclusion; they expressed both transgene-derived IgG and endogenous IgM intracellularly. Most of the B cells in transgenic mice expressed endogenous IgM, some of them expressed low levels of IgG on cell membranes. The transgenic mice, created in a strain not prone to SLE, expressed elevated serum IgG anti-DNA, and some developed clinical nephritis. The affinity of the spontaneously secreted IgG antibodies for dsDNA were similar in nephritic NZB x NZW F1 and transgenic mice. In contrast to the nontransgenic littermates, immunization of transgenic mice with murine DNA further enhanced serum levels of IgG anti-DNA in transgenic mice. Therefore, expression of transgene-encoded IgG anti-DNA mainly in the secreted form does not provide the signals necessary for allelic exclusion or self-tolerance. Expression of this Ig is sufficient to induce a mild form of autoimmune disease.
authors.affiliation: Department of Medicine, University of California, Los Angeles 90024.
authors.forename: B P
authors.initials: BP
authors.lastname: Tsao
authors.forename: K
authors.initials: K
authors.lastname: Ohnishi
authors.forename: H
authors.initials: H
authors.lastname: Cheroutre
authors.forename: B
authors.initials: B
authors.lastname: Mitchell
authors.forename: M
authors.initials: M
authors.lastname: Teitell
authors.forename: P
authors.initials: P
authors.lastname: Mixter
authors.forename: M
authors.initials: M
authors.lastname: Kronenberg
authors.forename: B H
authors.initials: BH
authors.lastname: Hahn
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D009393:Nephritis / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D014158:Transcription, Genetic
chemical_list: D000974:Antibodies, Antinuclear; D012333:RNA, Messenger