CHARACTERIZATION OF A MATURE BILE-DUCT ANTIGEN EXPRESSED ON A SUBPOPULATION OF BILIARY DUCTULAR CELLS BUT ABSENT FROM OVAL CELLS

Hybridomas were produced with immune spleen cells generated by immuniz ation of Balb/c mice with oval cell antigen (OC.2)-positive 17-day fet al liver cells isolated on antibody-coated magnetic beads. A primary s creen by indirect immunofluorescence on frozen sections of fetal and a dult liver identified several hybridomas secreting antibodies reactive with bile ducts and oval cells. One of these recognized an epitope, d esignated BD1, which was expressed on intrahepatic bile ducts in 16-da y fetal and adult rat liver and in liver from rats fed a choline-defic ient diet containing ethionine and rats treated with 2-acetylaminofluo rine, but was absent from morphologically defined oval cells induced b y a choline-deficient diet containing ethionine or by 2-acetylaminoflu orine. Double-labeling immunofluorescence analysis with monoclonal ant ibody BD1 and OV6, a monoclonal antibody that reacts uniformly with al l bile ducts and oval cells, revealed that BD1 expression on the intra hepatic bile ductular cells of normal adult rat liver was heterogeneou s with a major ductal cell population (60% to 70%) expressing high lev els of BD1 and a minor ductal cell population (30% to 40%) displaying undetectable or low levels of BD1 expression. Analysis of fetal liver demonstrated the presence of BD1-positive cells at day 16 of gestation on ductlike structures in contact with portal mesenchyme, an observat ion suggesting that expression of BD1 was associated with commitment o f hepatoblasts to a ductular lineage. Taken together, our findings sug gest that oval cells may be derived from an antigenically distinct sub population of bile ductal cells.