Mechanism of anti-DNA antibody formation. The functional modulation of helper T-subset plays the key role in both murine and human B-cell autosensitization.
The mechanism(s) of anti-DNA antibody formation was comparatively investigated using in vitro human and murine B-cell culture systems. T-cell homogenate (TH) from SLE patients converted normal human B-cells to anti-DNA specific antibody-forming plasma cells (anti-DNA-SPC) when cultured with calf thymic native DNA as antigen. TH of normal human donors suppressed the formation of anti-DNA-SPC from normal human B-cell cultures even when SLE TH and DNA were added to the cultures. B-cells derived from SLE patients were insensitive to normal human TH, and resulted in the formation of many anti-DNA-SPC. TH of young and old NZB mice stimulated the formation of anti-DNA-SPC from not only NZB but also C57BL/6 murine bone marrow cultures in the presence of DNA antigen. Human and murine TH, and both B-cell cultures were reciprocally combined to test whether xenogeneic TH stimulated B-cell cultures from different species. Xenogeneic TH was effective in triggering differentiation of xenogeneic B-cells with respect to anti-DNA-SPC. The elimination of helper T-subsets (Th) resulted in the generation of fewer anti-DNA-SPC, whereas the elimination of suppressor T-subsets (Ts) caused the formation of many anti-DNA-SPC. Among organ homogenates, e.g., liver, kidney and, brain, and T-cells from old NZB mice, TH was most effective in the stimulation of anti-DNA-SPC. The effective substance was sensitive to RNase-A, but resistant to pronase and DNase-I. Phenol extracted T-cell RNA retained its activity. We concluded that the functional modulation of helper T-cells, which reflects RNA molecules, could be the main etiology of autoantibody formation against DNA by both human and murine B-cells.
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*
D001323:Autoantibodies; D004247:DNA