Kaetzel C S, Robinson J K, Chintalacharuvu K R, Vaerman J P, Lamm M E
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8796-800. doi: 10.1073/pnas.88.19.8796.
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.
黏膜上皮细胞上的多聚免疫球蛋白受体（pIgR）在基底外侧表面结合二聚体IgA（dIgA），并介导dIgA向顶端表面的转运。利用稳定转染了pIgR cDNA的Madin-Darby犬肾上皮细胞，我们发现125I标记的大鼠抗二硝基苯基（DNP）dIgA（125I-dIgA）与DNP/生物素-牛血清白蛋白的可溶性免疫复合物（ICs）从基底外侧表面转运至顶端表面，然后释放。单体IgA免疫复合物未被转运，这与pIgR对多聚免疫球蛋白的特异性一致。顶端培养上清液中基本上所有的125I-dIgA都可被链霉亲和素沉淀，表明dIgA在转胞吞过程中仍与抗原结合。虽然dIgA和dIgA免疫复合物以相同的亲和力（解离常数约为8 nM）结合pIgR，但每个细胞上高亲和力结合位点的数量dIgA比dIgA免疫复合物多2至3倍。dIgA和dIgA免疫复合物的内吞程度与高亲和力结合位点的数量相关。细胞内dIgA和dIgA免疫复合物的SDS/PAGE分析表明，在这两种情况下，IgA在转运过程中均未降解。结果表明，游离dIgA和dIgA免疫复合物的上皮转胞吞途径相同。鉴于黏膜IgA浆细胞的高群体密度以及表达pIgR的黏膜上皮的巨大表面积，体内很可能发生IgA免疫复合物的显著局部转胞吞作用。这样一个过程将允许在可能形成IgA免疫复合物的黏膜部位直接清除它们，从而为IgA提供重要的防御功能。
