The contribution of I-Abm12 to phenotypic and functional alterations among T-cell subsets in NZB mice.
To further understand the contribution of I-A to the development of disease in murine lupus, we compared the incidence and/or titers of natural thymocytotoxic autoantibodies (NTAs), autoantibodies to red blood cells, gp70 immune complexes (gp70), antibodies to Sm, and rheumatoid factor in NZB (H-2d), NZB.H-2b and NZB.H-2bm12 mice. There were striking and significant differences among the three NZB strains in several of these parameters. NZB (H-2d) and NZB.H-2bm12 mice had a 100% incidence of NTA. In contrast, NZB.H-2b mice were found to have NTA in only 36% of animals at 8-10 months of age. Furthermore, the NTA titers of NZB.H-2bm12 mice were relatively low. There were also distinct differences between these strains with respect to the presence of antibodies to anti-erythrocytes (positive Coombs' test). NZB (H-2d) and NZB.H-2bm12 both had high titers of anti-erythrocyte autoantibodies (AEAs), whereas there was a delayed onset and lower titers in NZB.H-2b mice. Additionally, there was a dramatic increase in gp70 IC levels in NZB.H-2bm12 mice. In previous studies, NZB.H-2bm12 as well as NZB.H-2bm12 x NZB.H-2b F1 mice were found to produce high autoantibody titers to single-stranded (ss) and double-stranded (ds) DNA. Using unfractionated or fractionated splenic T cells (CD4+ CD8-, CD4- CD8+, or CD4-CD8-) from NZB.H-2b or NZB.H-2bm12 mice, we compared their relative abilities to cooperate with T-depleted splenocytes from NZB.H-2bm12 x NZB.H-2b F1 mice to produce antibodies to ss- and ds-DNA. Only T cells, including both CD4+ CD8- and CD4- CD8- populations, from NZB.H-2bm12 mice, were able to induce such autoantibody production among F1 splenocytes. Finally, marked alterations in splenic T cell subsets were found in NZB.H-2bm12 mice compared to NZB.H-2b mice, and to a lesser extent, in B6.C-H-2bm12 mice compared to C57BL/6 (H-2b) mice. These data further highlight the influence of I-A on autoimmunity and in particular the influence of the bm12 mutation on altering the natural history of disease expression in NZB mice.
Division of Rheumatology, Allergy and Clinical Immunology, University of California, School of Medicine, Davis 95616.
M
M
Naiki
S H
SH
Yoshida
Y
Y
Watanabe
S
S
Izui
A A
AA
Ansari
M E
ME
Gershwin
D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005802:Genes, MHC Class II; D006023:Glycoproteins / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D006388:Hemagglutinins / Q000097:blood; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D012217:Rheumatoid Factor / Q000097:blood; D017411:Ribonucleoproteins, Small Nuclear; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055517:snRNP Core Proteins
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D006023:Glycoproteins; D006183:H-2 Antigens; D006388:Hemagglutinins; D000949:Histocompatibility Antigens Class II; D017411:Ribonucleoproteins, Small Nuclear; C033589:glycoprotein gp70, murine serum; D055517:snRNP Core Proteins; D012217:Rheumatoid Factor