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

Abstract

Immunoglobulins (Igs) in mucosal secretions contribute to immune homeostasis by limiting access of microbial and environmental antigens to the body proper, maintaining the integrity of the epithelial barrier and shaping the composition of the commensal microbiota. The emergence of IgM in cartilaginous fish represented the primordial mucosal Ig, which is expressed in all higher vertebrates. Expansion and diversification of the mucosal Ig repertoire led to the emergence of IgT in bony fishes, IgX in amphibians, and IgA in reptiles, birds, and mammals. Parallel evolution of cellular receptors for the constant (Fc) regions of Igs provided mechanisms for their transport and immune effector functions. The most ancient of these Fc receptors is the polymeric Ig receptor (pIgR), which first appeared in an ancestor of bony fishes. The pIgR transports polymeric IgM, IgT, IgX, and IgA across epithelial cells into external secretions. Diversification and refinement of the structure of mucosal Igs during tetrapod evolution were paralleled by structural changes in pIgR, culminating in the multifunctional secretory IgA complex in mammals. In this paper, evidence is presented that the mutualistic relationship between the commensal microbiota and the vertebrate host provided the driving force for coevolution of mucosal Igs and pIgR.

B cells and their role in the teleost gut

“…In mammals, pIgR is expressed in the basolateral surface of mucosal and glandular epithelial cells and is able to transport both IgA and IgM across mucosal epithelial cells to the outer mucus layer. At the apical surface, pIgR is proteolytically cleaved, and subsequently, the extracellular domain of the pIgR (called secretory component (SC)) remains associated with IgA or IgM, creating a complex that is released in the mucus layer (Kaetzel, 2014). …”

“…However, as described above, teleost mucosal immunoglobulins are transported into mucus without the J chain. Although the mechanisms by which teleost immunoglobulins interact with the pIgR remain thus far a mystery, a theoretical model proposed by Kaetzel predicts that without J chain the interaction of IgT to pIgR is mediated by the binding of two domains of pIgR with the constant domain 3 of the IgT heavy chain (Kaetzel, 2014). In a similar vein, although the J chain interacts with IgM in amphibians, IgX multimerization and transport can be mediated without J chain association (Mussmann et al, 1996).…”

Adaptive immune responses at mucosal surfaces of teleost fish

“…The evolutionary origin of the mucosa-associated IgT is yet to be clarified, and its appearance in some lineages of bony fishes could be due to selection pressures arising from the necessity to protect the mucosal surfaces [47]. Further, IgT/Z shares many functional similarities with mammalian IgA [22].…”

The Structures of Secretory and Dimeric Immunoglobulin A

“…The most prominent mammalian mucosal antibody is Secretory (S) Immunoglobin (Ig) A, with the average human secreting grams each day. SIgA is a polymeric antibody, typically composed of two IgA monomers (although higher order polymers have been reported) linked through one joining-chain (JC) and bound by one secretory component (SC) (Donaldson et al, 2018;Flajnik, 2010;Kaetzel, 2014;Pabst and Slack, 2020).…”