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 Mymectomized BALB/c mouse with SP 2/0 murine myeloma cells. The LSA-1 isotype was IgG2b and kappa. LSA-1 Mras 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 sectio ns of liver in immunohistochemical analysis. Furthermore, the antigen recog nized with LSA-1 was highly expressed on the surface of a murine hepatoma c ell 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 cytotox ic activity on liver cell lines in the presence of a complement in vitro. F urthermore, injection of LSA-1 into mice-induced liver injury. These result s suggest that anti-liver autoantibody plays an important role in the induc tion of autoimmune hepatitis. Accordingly Mis antibody will be a useful too l for the analysis of the pathogenesis of autoimmune hepatitis. (C) 2001 Ac ademic Press.