• Gui Yang, Xiao-Rui Geng, Zhi-Qiang Liu, Jiang-Qi Liu, Xiao-Yu Liu, Ling-Zhi Xu, Huan-Ping Zhang, Ying-Xue Sun, Zhi-Gang Liu, and Ping-Chang Yang.
• From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China, the Brain Body Institute, McMaster University, Hamilton, Ontario L8N 4A6, Canada, and Longgang Central Hospital, Shenzhen 518116, China.
• J. Biol. Chem. 2015 May 15; 290 (20): 12858-67.

AbstractRestoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. B cells are involved in immune regulation. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation. This paper aims to elucidate the mechanism by which B cells restore the Ag-specific immune tolerance in an allergic environment. In this study, a B cell-deficient mouse model was created by injecting an anti-CD20 antibody. The frequency of tolerogenic dendritic cell (TolDC) was assessed by flow cytometry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The expression of thrombospondin-1 (TSP1) was assessed by quantitative real-time RT-PCR, Western blotting, and methylation-specific PCR. The results showed that B cells were required in the generation of the TGF-β-producing TolDCs in mice. B cell-derived TSP1 converted the latent TGF-β to the active TGF-β in DCs, which generated TGF-β-producing TolDCs. Exposure to IL-13 inhibited the expression of TSP1 in B cells by enhancing the TSP1 gene DNA methylation. Treating food allergy mice with Ag-specific immunotherapy and IL-13 antagonists restored the generation of TolDCs and enhanced the effect of specific immunotherapy. In conclusion, B cells play a critical role in the restoration of specific immune tolerance in an allergic environment. Blocking IL-13 in an allergic environment facilitated the generation of TolDCs and enhanced the therapeutic effect of immunotherapy. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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