Role of J Chain in Secretory Immunoglobulin Formation

Abstract

The joining (J) chain is a small polypeptide, expressed by mucosal and glandular plasma cells, which regulates polymer formation of immunoglobulin (Ig)A and IgM. J-chain incorporation into polymeric IgA (pIgA, mainly dimers) and pentameric IgM endows these antibodies with several salient features. First, a high valency of antigen-binding sites, which makes them suitable for agglutinating bacteria and viruses; little or no complement-activating potential, which allows them to operate in a noninflammatory fashion; and, most importantly, only J-chain-containing polymers show high affinity for the polymeric Ig receptor (pIgR), also known as transmembrane secretory component (SC). This epithelial glycoprotein mediates active external transfer of pIgA and pentameric IgM to exocrine secretions. Thus, secretory IgA (SIgA) and SIgM, as well as free SC, are generated by endoproteolytic cleavage of the pIgR extracellular domain. The secretory antibodies form the 'first line' of defence against pathogens and noxious substances that favour the mucosae as their portal of entry. The J chain is involved in creating the binding site for pIgR/SC in the Ig polymers, not only by determining the polymeric quaternary structure but apparently also by interacting directly with the receptor protein. Therefore, both the J chain and the pIgR/SC are key proteins in secretory immunity.

Human Plasma-derived Polymeric IgA and IgM Antibodies Associate with Secretory Component to Yield Biologically Active Secretory-like Antibodies

“…We first analyzed whether plasma-derived, polyclonal pIgA contained J chain, as this is a prerequisite for subsequent assembly with SC (24). Immunoblot analysis of various plasma IgA-enriched preparations confirmed that in addition to the major mIgA fraction, an SDS-resistant polymer-fraction was present that carried all three expected polypeptides, i.e.…”

25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production

“…Ch25h Ϫ/Ϫ mice had higher levels of mRNAs encoding the heavy chain of IgA (IgA H ) and the Ig joining chain (IgJ). The latter protein assembles monomeric IgA into a polymeric form and acts as a ligand for the Ig receptor that transports IgA across the mucosal epithelium (12). To confirm the microarray results, quantitative PCR (qPCR) was performed in the wild-type and mutant mice (Fig.…”

Polymeric immunoglobulin receptor

“…Moreover, most IgA-secreting plasma cells secrete the dimeric form of IgA, dimeric IgA (dIgA). Detailed investigation of the structure of dIgA has revealed the existence of the joining chain (Jchain) (11)(12)(13)(14), a 15-kDa acidic protein that contributes to the dimerization of IgA (15). The J-chain is critically important in the binding of dIgA to its receptor, pIgR (16)(17)(18)(19).…”