The liver is involved in the regulation of serum levels of IgA through the selective transport of circulating IgA into the bile, and in the removal of IgA-containing immune complexes and their transport through the hepatocytes into the bile. Recent evidence indicates that several types of receptors on hepatocytes are involved in this transport process. In addition to """"""""secretory component"""""""", a glycoprotein identified as a receptor for IgA on epithelial cells and on rodent hepatocytes, glycoprotein receptors and an as yet unidentified receptor specific for polymeric IgA are involved. The mechanisms of binding of mouse and human IgA of two subclasses and different molecular forms by mouse and human liver will be investigated in vitro. The specificity of the IgA receptor(s) will be determined by competitive binding assays to a particulate fraction of liver homogenates, to isolated plasma membranes, and to detergent-solubilized, affinity chromatography purified IgA receptors. The role of carbohydrates and the type of liver cells involved in the binding of IgA will be examined. Transport of immune complexes that contain in addition to IgA, also IgM or IgG antibodies will be examined with respect to their mechanism of hepatobiliary transport: The ability of immune complexes containing IgA, IgG or IgM to induce a subsequent immune response will be investigated. The fate and organ distribution of immune complexes that contain various immunoglobulin classes will be investigated in animals with mechanically impaired bile outflow or chemically induced liver damage. The planned studies may elucidate the incompletely characterized functions of serum IgA, which in humans represents an immunoglobulin class produced in larger quantities than IgG and IgM.
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