In this paper, we describe the production of a panel of monoclonal antibodies which define antigens which distinguish between hepatocytes and oval cells. These antibodies were obtained from hybridomas constructed from the spleens of mice immunized by a novel protocol designed to suppress response to unwanted or immunodominant epitopes. Of the antibodies obtained, four, 258.7, 270.11, 258.34, and 270.38, were directed to antigens of morphologically defined oval cells, while two, 258.26 and 270.26, defined cytoplasmic antigens of hepatocytes. Examination of frozen sections of normal, regenerating adult and fetal liver and livers from rats fed 2-acetylaminofluorene or ethionine in a choline-deficient diet indicates that morphologically defined oval cells may in fact comprise a phenotypically complex set of cells composed of at least three antigenically distinct subpopulations. The patterns of expression of the antigens defined by these antibodies suggest two possible pathways of liver cell differentiation.
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