Secretory Antibody Formation: Conserved Binding Interactions between J Chain and Polymeric Ig Receptor from Humans and Amphibians

Abstract

Abs of the secretory Ig (SIg) system reinforce numerous innate defense mechanisms to protect the mucosal surfaces against microbial penetration. SIgs are generated by a unique cooperation between two distinct cell types: plasma cells that produce polymers of IgA or IgM (collectively called pIgs) and polymeric Ig receptor (pIgR)-expressing secretory epithelial cells that mediate export of the pIgs to the lumen. Apical delivery of SIgs occurs by cleavage of the pIgR to release its extracellular part as a pIg-bound secretory component, whereas free secretory components are derived from an unoccupied receptor. The joining chain (J chain) is crucial in pIg/SIg formation because it serves to polymerize Igs and endows them with a binding site for the pIgR. In this study, we show that the J chain from divergent tetrapods including mammals, birds, and amphibians efficiently induced polymerization of human IgA, whereas the J chain from nurse shark (a lower vertebrate) did not. Correctly assembled polymers showed high affinity to human pIgR. Sequence analysis of the J chain identified two regions, conserved only in tetrapods, which by mutational analysis were found essential for pIgA-pIgR complexing. Furthermore, we isolated and characterized pIgR from the amphibian Xenopus laevis and demonstrated that its pIg binding domain showed high affinity to human pIgA. These results showed that the functional site of interaction between pIgR, J chain and Ig H chains is conserved in these species and suggests that SIgs originated in an ancestor common to tetrapods.

Expression of IgM, IgD, and IgY in a Reptile, Anolis carolinensis

“…In teleost fish that do not produce IgA, its function is fulfilled by IgM (45). Considering that IgM shares the same transport receptor with IgA (or IgX) in mammals and birds and Xenopus (46,47) and that it is highly expressed in the lizard intestine (Fig. 4), it is likely to play a role in mucosal immunity when IgA is absent.…”

“…The ␣ gene recently cloned from the gecko (15) was proposed to have originated from a recombination between the and genes, with the first two C H domains being derived from the C H 1-2 and the last two derived from C H 3-4, a scenario that also applies to bird ␣ and Xenopus IgX H chains (15). The hypothesis that ␣ originated from a recombination between the and genes explains why only IgM and IgA can form polymeric Abs and also why IgM and IgA share the same polymeric Ig receptor (46,47). Indeed, sequence comparisons of the gecko ␣ with the lizard and , show strikingly high similarities at the inferred protein level between the gecko ␣ C H 1-2 and the lizard C H 1-2 (59.0% identity), and between the gecko ␣ C H 3-4 and the lizard C H 3-4 (59.6% identity; supplemental Table II and supplemental Fig.…”

Mucosal Immunity: Induction, Dissemination, and Effector Functions

“…External transport of secretory antibodies is a fundamental biological phenomenon which has been preserved and enhanced throughout the phylogeny of tetrapods [22], probably because it is essential for the survival of particularly the mammalian species. The SIg system represents quantitatively the most important part of the antibody-dependent defence system of the body.…”

Coevolution of Mucosal Immunoglobulins and the Polymeric Immunoglobulin Receptor: Evidence That the Commensal Microbiota Provided the Driving Force

“…Despite the shorter length of pIgR in birds, reptiles, and amphibians, the association with the J chain subunit of polymeric IgX/A still appears to be required. Recombinant pIgR from the African frog (Xenopus laevis) was shown to bind with moderately high affinity to human polymeric IgA containing J chain, but not to monomeric IgA [125]. The affinity of Xenopus pIgR for human pIgA was improved when Xenopus J chain was substituted for human J chain in a chimeric polymeric IgA molecule.…”