title: Mechanism for enhanced external transfer of dimeric IgA over pentameric IgM: studies of diffusion, binding to the human polymeric Ig receptor, and epithelial transcytosis.
abstract: Transport of polymeric Igs (pIgA and pIgM) across secretory epithelia is mediated by the polymeric Ig receptor (pIgR), also known as the transmembrane secretory component. Compared with local production, external transfer of pIgA is favored 6- to 12-fold over that of pIgM on a molar basis. This transfer may be modulated at several levels: diffusion through matrix and basement membranes, ligand affinity for pIgR, and efficiency of epithelial transcytosis. To investigate these possibilities, we compared the ability of Madin-Darby canine kidney epithelial cells transfected with human pIgR to transport pIgA vs pIgM from the basolateral to the apical face, and examined the inhibitory effect of various filter types used for mounting of the monolayer. Binding data showed that pIgR bound pIgA and pIgM with similar affinity. Internalization of both ligands was fast and took place at similar rates; transcytosis was also found to be equally efficient at the molar level. Thus, the overall rate of transport across the epithelial monolayer was comparable for pIgA and pIgM, and was not further enhanced by ligand stimulation over a 20-fold increased concentration level. Conversely, pIgA had a considerable advantage over pIgM in passive diffusion assays performed in vitro. Moreover, in situ immunofluorescence staining showed retention of IgM over IgA and IgG in mucosal basement membrane zones, in contrast to the preferential epithelial uptake of IgA and, less so, IgM. The biologic consequences of the highly efficient epithelial pIg transport, and the diffusion advantage of pIgA over pIgM, are discussed in relation to the evolution and function of secretory Abs.
authors.affiliation: Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, The National Hospital, Rikshospitalet, Norway.
authors.forename: I B
authors.initials: IB
authors.lastname: Natvig
authors.forename: F E
authors.initials: FE
authors.lastname: Johansen
authors.forename: T W
authors.initials: TW
authors.lastname: Nordeng
authors.forename: G
authors.initials: G
authors.lastname: Haraldsen
authors.forename: P
authors.initials: P
authors.lastname: Brandtzaeg
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000276:immunology; D002460:Cell Line; D019281:Dimerization; D004285:Dogs; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism*; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism*; D007668:Kidney / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism
chemical_list: D007070:Immunoglobulin A; D007075:Immunoglobulin M; D011971:Receptors, Immunologic