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.