Secretory component: The polymeric immunoglobulin receptor: What's in it for the gastroenterologist and hepatologist?

Abstract The primary function of the SC-pIg system is to secrete pIgs into various external secretions. The cellular mechanism responsible for this transport is schematically depicted in Figure 5. Polymeric immunoglobulin A, which is synthesized by plasma cells that are part of the mucosa-associated lymphoid tissue, gains access to the SC on the albuminal surface of epithelial cells by diffusion from sites of synthesis in mucosae or enters the blood circulation and is cleared, largely by hepatic transport, into bile. The pIgA binds to SC on the abluminal surface of the epithelial cells (and probably hepatocytes) initially by noncovalent interactions that are saturable, reversible, and specific for pIgA and IgM. Subsequently, covalent interaction between SC and its ligand occurs to a variable degree in different species. The SC-IgA complex is endocytosed by the epithelial cell or hepatocyte and is transported across the cell into the external secretions by a microtubule-dependent vesicular transport mechanism. At some point during the transport, the complex is rendered soluble by proteolytic cleavage of the membrane-associated SC molecule to release the soluble sIgA into the gland lumen or the canaliculus. In the intestinal lumen, SC helps protect the sIgA molecule from proteolytic degradation. The sIgA may play a major role in the mucosal defense against pathogenic organisms or harmful antigens. The SC-pIg system differs from many of the other known receptor-ligand interactions in several important ways. First, the synthesis or expression of the receptor (SC), or both, are not regulated by the concentration of the ligand. Second, SC probably is not dissociated from its ligand or recycled to the cell surface as it is secreted in complex with its ligand (pIg) into the external secretions. Third, the interaction of pIgs with their receptor does not function to regulate an intracellular process, but results in transcellular transport of the ligand, which acts in the external environment. Fourth, after initial noncovalent, reversible binding between the receptor and its ligand, the interaction becomes covalent by the formation of disulfide linkages between SC and the pIg. Finally, SC is initially inserted into the abluminal domain of epithelial cells as an integral membrane protein and subsequently is proteolytically cleaved to a soluble molecule which is secreted by the cell. Thus, in contrast to many cell-surface receptor-ligand interactions in which the ligand is ultimately degraded and the receptor is conserved, the SC-pIgA interaction results in partial proteolytic degradation of the receptor and conservation of the ligand. Despite the wealth of information that has accumulated about this receptor-ligand system, a number of very important questions remain to be answered: How is the synthesis and expression of SC in tissues such as the intestine and the liver regulated? What determines how SC is expressed during normal differentiation? What are the cellular mechanisms responsible for the sorting of membrane SC to the abluminal domain of the plasma membrane and then rerouting of SC to and through the luminal plasma membrane? Where and how does the SC-pIg transcellular transport pathway diverge from other receptor-mediated endocytic pathways? What are the specific functions of the sIgA or secretory IgM after secretion into the extracellular environment? From the standpoint of pathophysiology of the liver and digestive organs, it is likely that full understanding of SC and SC-pIg interactions will greatly contribute to understanding of many fundamental aspects of the cellular biology of hepatocytes and intestinal epithelial cells. Moreover, important clues concerning the pathogenesis of major digestive tract diseases, e.g., malignancies and chronic inflammatory diseases, may lie in a better appreciation of SC and the secretory immune system. Thus, study of the SC-pIg system will likely continue to be a fruitful and exciting area of investigation for years to come.