TSP1-producing B cells restore Ag specific immune tolerance in an allergic environment [Cell Biology]

April 3rd, 2015 by Yang, G., Geng, X.-R., Liu, Z.-Q., Liu, J.-Q., Liu, X.-Y., Xu, L.-Z., Zhang, H.-P., Sun, Y.-X., Liu, Z.-G., Yang, P.-C.

To restore 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 is to be further investigated. 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 the methylation specific PCR. The results showed that B cells were required in the generation of the transforming growth factor (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 interleukin (IL)-13 inhibited the expression of TSP1 in B cells by enhancing the TSP1 gene DNA methylation. Treating food allergy mice with specific Ag 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 facilitates the generation of TolDCs and enhanced the therapeutic effect of immunotherapy.