Epithelial transcytosis of monomeric IgA and IgG cross-linked through antigen to polymeric IgA. A role for monomeric antibodies in the mucosal immune system.

ABSTRACT

We recently demonstrated that the polymeric IgR (pIgR) mediates epithelial transcytosis of immune complexes (IC) containing dimeric IgA (dIgA). In vivo, this "excretory" pathway could allow direct elimination of IgA IC at the mucosal sites where they are likely to form. In contrast, IC containing only monomeric IgA (mIgA) were not transported, consistent with the specificity of pIgR for polymeric IgA. However, the potential exists in vivo that monomeric Ig like mIgA or IgG could become associated through binding to multivalent Ag with IC containing dIgA, and that such mixed IC could act as ligands for pIgR. In the present work, using Madin-Darby canine kidney epithelial cells that express pIgR, we showed that 125I-labeled anti-DNP mIgA or IgG in the same IC with unlabeled dIgA antibody and DNP-BSA Ag was vectorially transported from the basolateral to the apical surface and then released. However, 125I-mIgA IC or 125I-IgG IC (without dIgA) and 125I-mIgA or 125I-IgG in the presence of dIgA antibody (but without Ag) were not transported, demonstrating the necessity for monomeric Ig to be in an IC with dIgA to be transported. Transcytosis of mixed mIgA/dIgA or IgG/dIgA IC was mediated by pIgR because no transport was observed in untransfected, wild-type Madin-Darby canine kidney cells lacking pIgR. The data demonstrate that mIgA and IgG can participate along with dIgA in the "excretory" pathway for local elimination of IgA IC, thus providing a means by which monomeric antibodies have the potential to participate in the mucosal immune system.