Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice

Mucosal surfaces are protected specifically by secretory immunoglobulin A ( SIgA) and SIgM generated through external translocation of locally produced dimeric IgA and pentameric IgM. Their active transport is mediated by the epithelial polymeric Ig receptor (pIgR), also called the transmembrane secr etory component. Paracellular passive external transfer of systemic and loc ally produced antibodies also provides mucosal protection, making the biolo gical importance of secretory immunity difficult to assess. Here we report complete lack of active external IgA and IgM translocation in pIgR knockout mice, indicating no redundancy in epithelial transport mechanisms. The kno ckout mice were of normal size and fertility but had increased serum IgG le vels, including antibodies to Escherichia coli, suggesting undue triggering of systemic immunity. Deterioration of their epithelial barrier function i n the absence of SIgA (and SIgM) was further attested to by elevated levels of albumin in their saliva and feces, reflecting leakage of serum proteins . Thus, SIgA did not appear to be essential for health under the antigen ex posure conditions of these experimental animals. Nevertheless, our results showed that SIgA contributes to maintenance of mucosal homeostasis. Product ion of SIgA might therefore be a variable in the initiation of human immuno pathology such as inflammatory bowel disease or gluten-sensitive enteropath y.