Abstract
Previously, ginsenoside metabolite compound K (C-K) was able to reduce B cell proliferation and serum anti-type II collagen (anti-CII) antibody to normal levels in mice with collagen-induced arthritis (CIA); however, the mechanism by which C-K restores B cell balance is unclear. In the present work, C-K treatment not only alleviated the polyarthritis index, swollen joint count, pathological scores of spleen and joints, spleen index, B cell proliferation and the level of serum antibodies (IgG1, IgG2a and anti-collagen II), but C-K treatment also restored B cell subsets including regulatory B cells, plasma cells, memory B cells, mature B cells, and follicular B cells in CIA mice. Interestingly, C-K did not change the expression level of immunoglobulin D-type B-cell receptor (IgD-BCR) but promoted IgD-BCR endocytosis. C-K treatment enhanced β-arrestin1 expression, facilitating the colocalization between IgD and β-arrestin1, as well as colocalization between IgD and adaptor protein 2 (AP2). Inhibition of the β-arrestin1-AP2 interaction with barbadin significantly reduced the ability of C-K to attenuate IgD-BCR plasma membrane localization. These results taken together depict that C-K ameliorates CIA in part by inhibiting B cell activation through the triggering of IgD-BCR internalization in a β-arrestin1-AP2 dependent manner.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (81202541, 81330081), the Anhui Provincial Natural Science Foundation for Distinguished Young Scholars (1808085J28), the Key Projects of Natural Science Research of Anhui Colleges and Universities (KJ2017A176), Anhui University Excellent Youth Talent Support Program (gxyqZD2017025), Innovation and Entrepreneurship Support Program for Returnees of Anhui Province, the Foundation for Young Academic Back-bone of Anhui Medical University, and the Grants for Young Talents of Anhui Medical University (2013).
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Qingtong Wang and Wei Wei designed the study. Mei Zhang, Shanshan Hu, Juan Tao, Weijie Zhou, Rui Wang, Yu Tai, and Feng Xiao performed the experiments. Mei Zhang and Qingtong Wang wrote the manuscript. All authors read and approved the final manuscript.
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Supplementary Figure 1. Typical HPLC chromatograms of C-K. Typical HPLC chromatogram of C-K under the isocratic condition were recorded at the absorption wavelength 205nm, the maximum peak appears at the peak time of 15.228 minutes, and the purity of C-K is over 99%.
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Zhang, M., Hu, S., Tao, J. et al. Ginsenoside compound-K inhibits the activity of B cells through inducing IgD-B cell receptor endocytosis in mice with collagen-induced arthritis. Inflammopharmacol 27, 845–856 (2019). https://doi.org/10.1007/s10787-019-00608-2
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DOI: https://doi.org/10.1007/s10787-019-00608-2