Synthesis and biliary secretion of immunoglobulins by rat liver.

In this manuscript, we have attempted to first present an overview of the fundamentals of IgA secretion into rat bile via a receptor mediated process which involves the formation of vesicles and their vectorial movement to the bile canaliculus by a microtubule network. This transcellular pathway is used by all IgA secreting cells. The process is unique in that the transport vesicles do not pass through the Golgi-lysosomal region of the cell and therefore the ligand is allowed to enter the secretions intact with a portion of its receptor providing protection against proteases in the external environment. We also have demonstrated that the liver provides an early response to intestinal luminal antigen presentation. Stimulated B cells that are produced in the Peyer's patches in rodents home first to the liver. Only after boosting and the establishment of long term immunity are specific antibody producing cells found in other organs such as the intestine. Data are presented which would suggest that non-receptor mediated Ig transport into bile is by passive transport across tight junctional complexes between liver cells and by fluid phase vesicles. This observation may account for the small but consistent amount of IgA and IgG unattached to receptors that are found in the bile in humans. Exciting new evidence would indicate that the tight junctions can be made leaky by modifications in the hormonal environment. These observations may have wide range implications for understanding of how a variety of compounds enter the external secretions.