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.
This work was supported by the Medical Research Council of Canada and was presented in part at the Annual Meetings of the Canadian Federation of Biological Societies, 1977.