Defective primary and secondary IgG responses to thymic-dependent antigens in autoimmune PN mice.
Palmerston North (PN) mice spontaneously develop autoimmune disease resembling SLE. Because immune responsiveness has not been defined in this strain, a study was designed to assay primary splenic plaque-forming cell (PFC) responses to thymus-dependent (TD) and thymus-independent (TI) Ag. Initial surveys of PN mice inoculated with the TD Ag SRBC showed adequate production of IgM PFC, but small numbers of IgG PFC were developed with polyspecific antiserum. In contrast, H-2-compatible DBA/1 control mice gave the expected responses to SRBC (IgG plaques elevated twofold compared with IgM plaques). PN mice had the usual responses to Ag that are largely TI; both PN and DBA/1 mice had active IgM and modest IgG responses to TNP-LPS and TNP-Ficoll. Additional experiments determined that PN mice had similar patterns of defective IgG responses to several different TD Ag (SRBC, horse RBC, and DNP-keyhole limpet hemocyanin). In each instance, the usual predominance of IgG1 plaques was absent, and total numbers of plaques developed with antisera specific for IgG isotypes were suppressed. Defective PN IgG production was evident as early as 3 wk of age, was not influenced by aging to 43 wk, and was not corrected by increasing the antigenic challenge 10-fold. PN spleen cells treated with monoclonal anti-Thy-1.2 and C were injected with pools of DBA/1 T cells into 850-rad irradiated (DBA/1 x PN)F1 hybrids. These recipients expressed low IgG1 responses to SRBC, suggesting that the B cell-containing fraction that was not lysed by anti-Thy-1.2 transferred the PN defect. PN mice, which do not respond to TD Ag with active IgG production, contradict the proposal that autoimmunity is associated with hyper-responsiveness to TD and TI Ag.
Walker
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Rheumatology Section, Veterans Administration Medical Center, Columbia, MO 65201.
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001789:Blood Group Antigens / Q000276:immunology*; D005260:Female; D006462:Hemolytic Plaque Technique; D006736:Horses; D007116:Immunization, Passive; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007136:Immunoglobulins / Q000032:analysis; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007700:Kinetics; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D012756:Sheep; D013045:Species Specificity; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000276:immunology*
D000955:Antigens, T-Independent; D001789:Blood Group Antigens; D007074:Immunoglobulin G; D007136:Immunoglobulins