Anti-Sm autoantibodies in MRL mice: in vitro detection and generation of antibody-forming cells.
Antibodies to the nuclear antigen SM are specific for systemic lupus erythematosus in humans and mice. In order to study the cellular mechanisms of anti-Sm generation, a hemolytic plaque assay to identify and enumerate lymphocytes secreting anti-Sm has been developed by using SRBC coated with purified Sm by a modified carbodiimide technique. Anti-Sm-specific PFC were found in MRL/Mp-Ipr/Ipr and MLR/Mp- +/+ mice whose sera contained anti-Sm, but were never detected in anti-Sm-negative MRL mice or in normals. Spleen cells from anti-Sm-positive MRL/Mp-Ipr/Ipr mice generated anti-Sm PFC spontaneously after 4 days of in vitro culture, whereas cells from normal mice or anti-Sm-negative MRL mice were never observed to produce spontaneous anti-Sm, even when cultured in the presence of bacterial lipopolysaccharide. The generation of anti-Sm by MRL cells in vitro was found to be dependent on the presence of T cells, but the ability of cells from individual MRL mice to generate anti-Sm appeared to be limited by the availability of Sm-specific B cell precursors and not due to a relative absence of T cells capable of providing help for the anti-Sm response. Analysis at the cellular level of the in vitro generation of a disease-specific autoantibody by using the methods described should facilitate understanding of mechanisms of autoreactivity.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000302:isolation & purification*; D000917:Antibody Formation; D000921:Antibody-Producing Cells / Q000276:immunology; D001323:Autoantibodies / Q000302:isolation & purification*; D001327:Autoimmune Diseases / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008211:Lymphocyte Cooperation; D051379:Mice; D009698:Nucleoproteins / Q000276:immunology*; D012261:Ribonucleoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D009698:Nucleoproteins; D012261:Ribonucleoproteins