The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA.
The polymeric immunoglobulin receptor (pIgR) on mucosal epithelial cells binds dimeric IgA (dIgA) on the basolateral surface and mediates transport of dIgA to the apical surface. Using Madin-Darby canine kidney epithelial cells stably transfected with pIgR cDNA, we found that soluble immune complexes (ICs) of 125I-labeled rat monoclonal antidinitrophenyl (DNP) dIgA (125I-dIgA) and DNP/biotin-bovine serum albumin were transported from the basolateral to the apical surface and then released. Monomeric IgA ICs were not transported, consistent with the specificity of pIgR for polymeric immunoglobulins. Essentially all the 125I-dIgA in apical culture supernatants was streptavidin precipitable, indicating that dIgA remained bound to antigen during transcytosis. While both dIgA and dIgA ICs bound pIgR with equal affinity (Kd approximately 8 nM), the number of high-affinity binding sites per cell was 2- to 3-fold greater for dIgA than for dIgA ICs. The extent of endocytosis of dIgA and dIgA ICs was correlated with the number of high-affinity binding sites. SDS/PAGE analysis of intracellular dIgA and dIgA ICs demonstrated that in both cases IgA remained undegraded during transport. The results suggest that the pathways of epithelial transcytosis of free dIgA and dIgA ICs are the same. Given the high population density of mucosal IgA plasma cells and the enormous surface area of pIgR-expressing mucosal epithelium, it is likely that significant local transcytosis of IgA ICs occurs in vivo. Such a process would allow direct elimination of IgA ICs at the mucosal sites where they are likely to form, thus providing an important defense function for IgA.
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
C S
CS
Kaetzel
J K
JK
Robinson
K R
KR
Chintalacharuvu
J P
JP
Vaerman
M E
ME
Lamm
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D000941:Antigens / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D004285:Dogs; D004705:Endocytosis; D004848:Epithelium / Q000378:metabolism*; D007070:Immunoglobulin A / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D011971:Receptors, Immunologic / Q000378:metabolism*; D012635:Secretory Component / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D000941:Antigens; D007070:Immunoglobulin A; D046911:Macromolecular Substances; D011971:Receptors, Immunologic; D012635:Secretory Component