MZB1 promotes the secretion of J-chain–containing dimeric IgA and is critical for the suppression of gut inflammation

Ermeng Xiong, Yingqian Li, Qing Min, Chaoqun Cui, Jun Liu, Rongjian Hong, Nannan Lai, Ying Wang, Jiping Sun, Ryohtaroh Matsumoto, Daisuke Takahashi, Kouji Hase, Reiko Shinkura, Takeshi Tsubata, Ji Yang Wang

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5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13480-13489
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number27
DOIs
Publication statusPublished - 2019 Jan 1

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Keywords

  • Chaperone
  • Gut homeostasis
  • Heavy chain tailpiece
  • Immunoglobulin A
  • J chain
  • Molecular

ASJC Scopus subject areas

  • General

Cite this

Xiong, E., Li, Y., Min, Q., Cui, C., Liu, J., Hong, R., Lai, N., Wang, Y., Sun, J., Matsumoto, R., Takahashi, D., Hase, K., Shinkura, R., Tsubata, T., & Wang, J. Y. (2019). MZB1 promotes the secretion of J-chain–containing dimeric IgA and is critical for the suppression of gut inflammation. Proceedings of the National Academy of Sciences of the United States of America, 116(27), 13480-13489. https://doi.org/10.1073/pnas.1904204116