The anti-erythrocyte autoimmune response of NZB mice. Identification of two distinct autoantigens.
With age, New Zealand black (NZB) mice spontaneously develop anti-mouse red blood cell (RBC) autoantibodies resulting in the development of autoimmune haemolytic anemia (AIHA). Previously, we characterized a panel of monoclonal autoantibodies derived from unimmunized, adult NZB mice. One of these antibodies (G8) was shown to be pathogenic, inducing AIHA in a non-autoimmune-prone mouse strain (BALB/c). Using G8, and two other antibodies from our panel, we have characterized two distinct autoantigens on the surface of mouse RBCs. The autoantigen, historically referred to as antigen X (AgX), was found to be partially hidden on the surface of the mouse RBC because glycosidase treatment or mild digestion with proteinase K resulted in increased reactivity with autoantibodies. One of the monoclonal antibodies (3H5G1) was found to immunoprecipitate a 110,000 MW protein identified as the erythrocyte anion transporter (band 3) whereas the pathogenic antibody (G8) as well as a third monoclonal antibody (2E6m) were shown to immunoprecipitate a 60,000 MW protein that was not reactive with the anti-band 3 serum. Finally, we show that the autoantigen recognized by G8 is expressed on differentiated mouse erythroleukaemia (MEL) cells. The results suggest that a protein distinct from band 3 can serve as a target for AIHA in NZB mice.
Diiulio
N A
NA
Department of Immunology, Cleveland Clinic Foundation, OH, USA.
Fairchild
R L
RL
Caulfield
M J
MJ
D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology*; D000818:Animals; D001324:Autoantigens / Q000097:blood*; D002850:Chromatography, Gel; D019286:Endopeptidase K / Q000494:pharmacology; D000939:Epitopes / Q000032:analysis; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology*; D006026:Glycoside Hydrolases / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D011233:Precipitin Tests; D013010:Sonication
D001324:Autoantigens; D000939:Epitopes; D006026:Glycoside Hydrolases; D019286:Endopeptidase K