Murine graft vs host disease. A model for study of mechanisms that generate autoantibodies to ribonucleoproteins.
We established chronic graft vs host disease in (BALB/c x A/J) F1 mice with the injection of lymphoid cells from the parental A/J strain. These animals developed glomerulonephritis, forefoot edema, alopecia, splenomegaly, and lymphadenopathy to various degrees, and all developed antinuclear antibodies. To determine whether these antibodies were directed against the small nuclear ribonucleoprotein (snRNP) particles that are characteristic targets for autoimmune responses in human rheumatic diseases, sera were studied in the 32P immunoprecipitation and immunoblotting assays. Among 20 mice, antibodies to snRNP developed in 10. These antibodies usually reached maximal levels about 4 wk after induction of graft vs host disease and generally fell thereafter. However, two mice developed antibodies to snRNP between the 10th and 20th wk of follow-up. Sera from six mice strongly recognized the U1 snRNP and an additional serum strongly bound both the U1 and U3 particles. Several sera contained lower levels of antibodies specific for the U3 and possibly pre-U2 snRNP particles. In immunoblots, sera that immunoprecipitated the U1 snRNP bound epitopes located on its 70,000 Da, A, B'/B, and/or C polypeptides. Sera that immunoprecipitated the U3 snRNP recognized a 34,000-Da polypeptide. These polypeptides are known to bear the autoantigenic epitopes that are recognized by human sera containing anti-U1 RNP and anti-U3 RNP autoantibodies. We conclude that chronic graft vs host disease in mice provides a model for the study of the autoimmune responses that characterize human diseases such as mixed connective tissue disease, scleroderma, and SLE.
Gelpi
C
C
Department of Immunology, Hospital de la Santa Cruz y San Pablo, Barcelona, Spain.
Rodriguez-Sanchez
J L
JL
Martinez
M A
MA
Craft
J
J
Hardin
J A
JA
D000818:Animals; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000096:biosynthesis*; D001666:Binding Sites, Antibody; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology*; D007118:Immunoassay; D051379:Mice; D008805:Mice, Inbred A; D011233:Precipitin Tests; D012342:RNA, Small Nuclear / Q000276:immunology* / Q000302:isolation & purification
D001323:Autoantibodies; D012342:RNA, Small Nuclear