Abstract
Transcytosis of polymeric IgA and IgM from the basolateral surface to the apical side of the epithelium and subsequent secretion into mucosal fluids are mediated by the polymeric immunoglobulin receptor (pIgR). Secreted IgA and IgM have vital roles in mucosal immunity in response to pathogenic infections. Binding and recognition of polymeric IgA and IgM by pIgR require the joining chain (J chain), a small protein essential in the formation and stabilization of polymeric Ig structures. Recent studies have identified marginal zone B and B1 cell-specific protein (MZB1) as a novel regulator of polymeric IgA and IgM formation. MZB1 might facilitate IgA and IgM transcytosis by promoting the binding of J chain to Ig. In this review, we discuss the roles of pIgR in transcytosis of IgA and IgM, the roles of J chain in the formation of polymeric IgA and IgM and recognition by pIgR, and focus particularly on recent progress in understanding the roles of MZB1, a molecular chaperone protein.
Highlights
immunoglobulin A (IgA) forms dimers [58], whereas immunoglobulin M (IgM) forms pentamers and sometimes polymers of even higher orders [59]. This process of immunoglobulin polymerization is mediated by a special protein called joining chain (J chain) that binds to heavy chains of IgA and IgM through disulfide bonds at their C-terminal tailpieces [60]
Serum IgA levels were markedly increased in polymeric immunoglobulin receptor (pIgR)−/− mice [74,75]. These results demonstrated the essential roles of pIgR in transcytosis of IgA into the intestinal lumen, yet a small amount of IgA may be secreted via other pathways
Apart from its role in IgM assembly, data from our study suggested that marginal zone B and B1 cell-specific protein (MZB1) may function as a molecular chaperone in dimerization of J chain-containing IgA [148], which is a prerequisite for the recognition of IgA by pIgR
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Polymerized IgA, and to a lesser extent IgM, protect the mucosal surfaces from infection. The polymeric immunoglobulin receptor (pIgR) recognizes the J chain region of polymerized IgA and IgM and transports the antibodies across the epithelial cell. Since its function was first discovered in the 1980s, J chain, along with the molecular details of Ig polymerization, has largely been overlooked in the field of immunological research. It was only in the last decade when researchers started to take notice of marginal zone B and B1 cell-specific protein (MZB1) [5,6,7], a novel regulator of J chain-mediated Ig polymerization that precedes pIgR-mediated transcytosis. We further highlight the proposed roles of MZB1 in the polymerization of IgA and IgM and briefly summarize the latest reports that have implicated MZB1 in human diseases
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