| First Author | Xiong E | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 27 | Pages | 13480-13489 |
| PubMed ID | 31127044 | Mgi Jnum | J:277172 |
| Mgi Id | MGI:6317284 | Doi | 10.1073/pnas.1904204116 |
| Citation | Xiong E, et al. (2019) MZB1 promotes the secretion of J-chain-containing dimeric IgA and is critical for the suppression of gut inflammation. Proc Natl Acad Sci U S A 116(27):13480-13489 |
| abstractText | IgA is the most abundantly produced antibody in the body and plays a crucial role in gut homeostasis and mucosal immunity. IgA forms a dimer that covalently associates with the joining (J) chain, which is essential for IgA transport into the mucosa. Here, we demonstrate that the marginal zone B and B-1 cell-specific protein (MZB1) interacts with IgA through the alpha-heavy-chain tailpiece dependent on the penultimate cysteine residue and prevents the intracellular degradation of alpha-light-chain complexes. Moreover, MZB1 promotes J-chain binding to IgA and the secretion of dimeric IgA. MZB1-deficient mice are impaired in secreting large amounts of IgA into the gut in response to acute inflammation and develop severe colitis. Oral administration of a monoclonal IgA significantly ameliorated the colitis, accompanied by normalization of the gut microbiota composition. The present study identifies a molecular chaperone that promotes J-chain binding to IgA and reveals an important mechanism that controls the quantity, quality, and function of IgA. |
