Defects in antigen-specific immune tolerance in continuous B cell lines from autoimmune mice.
B cell hyperactivity and resistance to tolerance induction are well-recognized immunologic abnormalities associated with both human and murine models of systemic lupus erythematosus. Studies evaluating the role of B cells in these defects have been complicated by the difficulties of consistently isolating large numbers of B cells from T cells and other host-derived regulatory factors. We have recently developed continuous cell lines of B lymphocytes with a high degree of specificity for the antigen dinitrophenyl (DNP) from both New Zealand black times New Zealand white F1 hybrid (BWF1) and BALB/c mice, and we used them to study intrinsic B cell defects in autoimmunity. We found that the kinetics of the immune response to the antigen DNP-Ficoll of both the BWF1 and BALB/c B cell lines are not different. In addition, the BWF1 cell lines, like the BALB/c cell lines and normal B cells, require nonspecific T cell-derived factors as well as antigen to produce an immune response. Tolerance was tested in the BWF1 B cells by preincubating them with DNP-murine IgG2a (MGG), which can induce tolerance in BALB/c cell line lymphocytes. The BWF1 B cell lines were resistant to tolerance induction by DNP-MGG and required 50-fold higher dose of DNP-MGG than BALB/c cell lines for suppression. They were also relatively resistant to tolerance with trinitrophenyl-d-glutamyl lysine. Thus, DNP-specific B cells from autoimmune mice have an inherent defect in tolerance induction.
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004136:Dinitrobenzenes / Q000276:immunology; D004151:Dipeptides / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006241:Haptens; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D011919:Rats, Inbred Strains; D014301:Trinitrobenzenes / Q000276:immunology
D000941:Antigens; D004136:Dinitrobenzenes; D004151:Dipeptides; D000939:Epitopes; D006241:Haptens; D007074:Immunoglobulin G; D014301:Trinitrobenzenes; C049879:trinitrophenylglutamyllysine