Regulation of the autoimmune plaque-forming cell response to single-strand DNA (sDNA) in vitro.
We have shown that young autoimmune and normal strain mice possess autoantigen-sensitive cells potentially capable of producing anti-sDNA autoantibody in the absence of normal regulatory mechanisms in vitro. In certain strains such as B/W mice, these regulatory mechanisms presumably break down with increasing age, and autoimmunity develops. These regulatory mechanisms might consist of sDNA, T cells, or some combination of these since both of these agents suppressed the anti-sDNA PFC response in vitro. The sDNA may have inhibited PFC development by a receptor blockade mechanism since i) spleen cells pulsed with sDNA for short periods and then washed were suppressed after 5 days of culture; ii) treatment of these blocked cells with trypsin and DNase I restored the anti-sDNA response; iii) the PFC remaining in partially blocked cultures were of lower avidity than PFC in unblocked cultures; and iv) the target of sDNA may be a B cell. Thymocytes and splenic T cells suppressed the anti-sDNA response but not the anti-SRBC response in vitro in a dose-dependent manner. The suppressive capacity of thymus cells did not decline with age in B/W mice. In addition, thymus cells activated by competing foreign antigens could also suppress the anti-sDNA response. The relationship between these modes of regulating autoreactivity remains to be investigated.
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology*; D001323:Autoantibodies; D001324:Autoantigens; D002478:Cells, Cultured; D004247:DNA / Q000494:pharmacology; D004277:DNA, Single-Stranded / Q000276:immunology* / Q000494:pharmacology; D003851:Deoxyribonucleases / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006462:Hemolytic Plaque Technique; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014357:Trypsin / Q000494:pharmacology
D001323:Autoantibodies; D001324:Autoantigens; D004277:DNA, Single-Stranded; D004247:DNA; D003851:Deoxyribonucleases; D014357:Trypsin