Cellular interactions for the in vitro production of anti-chromatin autoantibodies in MRL/Mp-lpr/lpr mice.
Anti-chromatin autoantibodies are spontaneously produced by autoimmune but not by normal mice. An in vitro system was developed to study the cellular mechanisms of anti-chromatin production in MRL/Mp-lpr/lpr (MRL/lpr) mice. In such cultures, spleen cells from MRL/lpr mice with active autoimmune disease generated substantial amounts of anti-chromatin, as measured by ELISA of culture supernatants and by ELISA spot assay of anti-chromatin-producing cells. In vitro production of anti-chromatin autoantibodies was independent of T cells, even when spleen cells from animals as young as 1 month were examined. In contrast, anti-Sm production under the same conditions was highly T cell dependent. Macrophages and/or macrophage-derived factors were necessary for the in vitro production of anti-chromatin autoantibodies. The lack of anti-chromatin production by cells from nonautoimmune mice could not be ascribed to the presence of suppressor cells. These studies indicate that individual autoantibodies may arise through distinct cellular mechanisms in systemic lupus erythematosus mice. MRL/lpr mice develop global T lymphocyte deficiency along with their autoimmunity. The progressive increase in relatively thymus independent antibodies such as anti-chromatin is consistent with the lack of functional T lymphocytes in aging MRL/lpr mice.
Fisher
C L
CL
Department of Biochemistry, University of North Carolina School of Medicine, Chapel Hill 27599-7280.
Shores
E W
EW
Eisenberg
R A
RA
Cohen
P L
PL
D000375:Aging; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002843:Chromatin / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007111:Immunity, Cellular; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000974:Antibodies, Antinuclear; D002843:Chromatin