Investigations of intrinsic abnormalities in DNA-specific B lymphocytes from autoimmune mice.
In murine models of systemic lupus erythematosus and in many humans with SLE, antibodies against native DNA (dsDNA) are a major contributor to the pathogenesis of the disease. Loss of self-tolerance to the DNA antigen may be associated with B-cell defects or regulatory cell dysfunction. We have developed B-cell lines with specificity for the antigen DNA, from both the autoimmune BWF1 mouse strain and from the non-autoimmune BALB/c strain, to use in the investigation of inherent B-cell defects in autoimmunity. Six BWF1 cell lines and five BALB/c cell lines which are free of Thy1.2+ cells and esterase positive cells, and have between 35 and 89% rosetting with dsDNA-SRBC targets, have been propagated in vitro for 24-36 months. The cells are non-malignant, growth-factor dependent and have no antigen or mitogen in the growth medium. Lyt-1 positive cells are found in the cell lines, but Lyt-1 negative cells are also present. They respond to the antigen DNA-HRBC when EL-4 supernatant is present in culture, and the peak of the plaque-forming cell (PFC) response is the same for both strains. When cells from both strains are cultured with varying amounts of T-cell factors, there is no difference in spontaneous antibody-forming cell (AFC) formation or in response to anti-mu stimulation between BWF1 and BALB/c strains. BALB/c spleen cells do not respond to DNA-HRBC in this culture system, but BWF1 spleen cells, as well as cell line cells from both strains, respond to this antigen. T cells from non-responding BALB/c spleen and responding BWF1 spleen are able to suppress the immune response to DNA-HRBC of cell line B cells from both strains. Propagating B-cell lines in the presence of DNA for 2 weeks stimulates BWF1 cell line cells, but suppresses the response of BALB/c cell lines to antigen.
Aldo-Benson
M
M
Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.
D000818:Animals; D000950:Antigens, Ly; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004247:DNA / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000950:Antigens, Ly; D001323:Autoantibodies; D001324:Autoantigens; D004247:DNA