Molecular and cellular aspects of the secretory immunoglobulin system*

Adaptive immunological protection of mucous membranes is provided mainly by secretory IgA antibodies. Such "first line" defence is accomplished through a unique cooperation between the mucosal B-cell system and the secretory component (SC) expressed basolaterally on glandular epithelial cells. This transmembrane glycoprotein is quantitatively the most important receptor of the immune system because it is responsible for external transport of locally produced polymeric IgA (pIgA), which is the major product of humoral immunity. Transmembrane SC belongs to the Ig supergene family and functions as a general pIg receptor, also mediating the external translocation of pentameric IgM to form secretory IgM. The B cells responsible for local pIg production are initially stimulated in lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine, from which they migrate as memory cells to exocrine tissues all over the body. Mucous membranes are thus furnished with secretory antibodies in an integrated way, ensuring a variety of specificities at every secretory site. There is currently great interest in exploiting this integrated or "common" mucosal immune system for oral vaccination against pathogenic infectious agents. However, much remains to be learned about mechanisms for antigen uptake and processing necessary to elicit mucosal immunity as well as the molecular biology and cytokine regulation of SC-dependent pIg transport. Moreover, evidence is emerging for the existence of subcompartmentalization in the mucosal immune system, particularly a dichotomy in cellular migration between the gut and the upper airway, which may complicate the design of efficient local vaccines.