@article{7ca1466c1e154eefb711466b364d7285,
title = "MZB1 promotes the secretion of J-chain–containing dimeric IgA and is critical for the suppression of gut inflammation",
abstract = "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 α-heavy-chain tailpiece dependent on the penultimate cysteine residue and prevents the intracellular degradation of α-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.",
keywords = "Chaperone, Gut homeostasis, Heavy chain tailpiece, Immunoglobulin A, J chain, Molecular",
author = "Ermeng Xiong and Yingqian Li and Qing Min and Chaoqun Cui and Jun Liu and Rongjian Hong and Nannan Lai and Ying Wang and Jiping Sun and Ryohtaroh Matsumoto and Daisuke Takahashi and Koji Hase and Reiko Shinkura and Takeshi Tsubata and Wang, {Ji Yang}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank Prof. Michel Nussenzweig for providing the B1-8hi mice; Lumin Zhang for excellent technical assistance; Jing Qian for cell sorting; Fudan University Animal facility for maintaining the mice; and the members in the Department of Immunology for helpful discussions. This work was supported by National Basic Research Program of China Grant 2015CB943300 (to J.-Y.W.); National Natural Science Foundation of China Grants 81373129 and 81571529 (to J.-Y.W.); and Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (C) 17K08878 (to J.-Y.W.). Funding Information: We thank Prof. Michel Nussenzweig for providing the B1-8hi mice; Lumin Zhang for excellent technical assistance; Jing Qian for cell sorting; Fudan University Animal facility for maintaining the mice; and the members in the Department of Immunology for helpful discussions. This work was supported by National Basic Research Program of China Grant 2015CB943300 (to J.-Y.W.); National Natural Science Foundation of China Grants 81373129 and 81571529 (to J.-Y.W.); and Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (C) 17K08878 (to J.-Y.W.). Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All rights reserved.",
year = "2019",
doi = "10.1073/pnas.1904204116",
language = "English",
volume = "116",
pages = "13480--13489",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "27",
}