Cytotoxic effect of an anti-liver monoclonal autoantibody obtained after neonatal thymectomy in mice.
A monoclonal autoantibody, LSA-1, against murine liver antigen was obtained by fusing spleen cells from a neonatally thymectomized BALB/c mouse with SP2/0 murine myeloma cells. The LSA-1 isotype was IgG2b and kappa. LSA-1 was specific to the liver, especially, to a liver-specific membrane lipoprotein (LSP) fraction. By Western blotting analysis, LSA-1 mainly detected a 100 kDa protein of LSP fraction. LSA-1 stained cytoplasm of the cryostat sections of liver in immunohistochemical analysis. Furthermore, the antigen recognized with LSA-1 was highly expressed on the surface of a murine hepatoma cell line, MH134, slightly on a murine normal liver cell line, C1469, and on freshly prepared hepatocytes, but not on spleen cells. LSA-1 had a cytotoxic activity on liver cell lines in the presence of a complement in vitro. Furthermore, injection of LSA-1 into mice-induced liver injury. These results suggest that anti-liver autoantibody plays an important role in the induction of autoimmune hepatitis. Accordingly, this antibody will be a useful tool for the analysis of the pathogenesis of autoimmune hepatitis.
Yoshida
Y
Y
Department of Immunology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, 807-8555, Japan.
Myozaki
M
M
Kuroda
E
E
Yamashita
U
U
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology* / Q000302:isolation & purification; D005591:Chemical Fractionation; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods; D022781:Hepatocytes / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013934:Thymectomy; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens