Breaking of tolerance to native DNA in nonautoimmune mice by immunization with natural protein/DNA complexes.
A major event in the pathogenesis of systemic lupus erythematosus (SLE) is the breaking of tolerance to native DNA and the appearance of IgG anti-double-stranded (ds) DNA antibodies. The mechanisms of the losing of tolerance are not well understood. Continuous efforts have been made in the past to induce anti-native DNA IgG autoantibodies in non-autoimmune animals but the relevance of the approaches used to what happens in spontaneous disease is unclear. We succeeded in breaking tolerance to native DNA in nonautoimmune-prone BALB/c mice by immunization with natural DNA/protein complexes. These complexes included nucleosomes, crude commercial histone and nucleohistone preparations. The anti-dsDNA IgG response lasted for more than an year. IgG deposition in the kidneys of the animals was repeatedly shown. As DNA-specific B cells behave in many ways as non-autoreactive B cells, we suggest that the activity of the self-reactive B lymphocytes could be selectively inhibited in a way that mimics a physiological mechanism controlling the magnitude and duration of the IgG antibody response to foreign antigens.
Voynova
E N
EN
Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Tchorbanov
A I
AI
Todorov
T A
TA
Vassilev
T L
TL
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood*; D004247:DNA / Q000276:immunology*; D005260:Female; D006657:Histones; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D009707:Nucleosomes; D011498:Protein Precursors; D017634:Self Tolerance; D014452:Ubiquitins
D000974:Antibodies, Antinuclear; D006657:Histones; D007074:Immunoglobulin G; D009707:Nucleosomes; D011498:Protein Precursors; D014452:Ubiquitins; C045677:ubiquitin precursor; D004247:DNA