Epithelial Transport of IgA Immune Complexes

Abstract

IgA has traditionally been considered to function mainly as an immunological barrier or “antiseptic paint” along the lumenal surface of a mucous membrane, as in the respiratory or intestinal tracts¹. In this way, IgA antibody serves to prevent foreign macromolecules or microorganisms from adhering to or penetrating the lining epithelium. In contrast, the fate of IgA immune complexes that form within the mucous membrane proper has not received much attention, either conceptually or experimentally. Such complexes could form, for example, if macromolecular antigens or fragments thereof are able to penetrate the mucosal epithelium to some extent, or if antigens derived from an infectious agent replicating within the mucous membrane combine with IgA antibodies secreted from local plasma cells. From their formation in the lamina propria of the mucous membrane, such IgA immune complexes could reach the circulation, where they could be removed by the mononuclear phagocyte system or, in certain species such as the rat but not so much in humans, by transport into the bile². On the other hand, a more efficient path of removal of IgA immune complexes from the lamina propria would be direct passage across the neighboring mucosal lining cells via the same path normally used to transport free IgA into external secretions: IgA binds to the polymeric immunoglobulin receptor, secretory component, on the basolateral surface of the epithelial cell, after which the complex is endocytosed and transported through the epithelial cell into the secretions.