Xu Xia, Meng Qinghong, Erben Ulrike, Wang Peigang, Glauben Rainer, Kühl Anja A, Wu Hao, Ma Chung Wah, Hu Minghua, Wang Yuanyuan, Sun Wei, Jia Junying, Wu Xinyi, Chen Wei, Siegmund Britta, Qin Zhihai
Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Cell Mol Immunol. 2017 Jul;14(7):597-606. doi: 10.1038/cmi.2015.103. Epub 2016 May 2.
Myeloid-derived suppressor cells (MDSCs) are well known for their capacity to suppress antitumor T-cell responses, but their effects on B-cell function and antibody production remain unclear. Here, we found that MDSCs that accumulated around the germinal center in the spleen of tumor-bearing mice co-located with B cells. In the presence of MDSCs, the antibody reaction to a surrogate antigen was significantly enhanced in mice, especially the immunoglobulin (Ig)A subtype. Co-culture with MDSCs promoted both proliferation and differentiation of B cells into IgA-producing plasma cells in vitro. Interestingly, the cross talk between MDSCs and B cells required cell-cell contact. MDSCs from tumor necrosis factor receptor (TNFR) 2 mice, but not from TNFR1 mice, failed to promote B-cell responses. Further investigation suggested that interleukin-10 and transforming growth factor-β1 were crucial for the MDSC-mediated promotion of IgA responses. These results demonstrate a novel mechanism of MDSC-mediated immune regulation during tumor growth.
髓源性抑制细胞（MDSCs）以其抑制抗肿瘤T细胞反应的能力而闻名，但其对B细胞功能和抗体产生的影响仍不清楚。在这里，我们发现荷瘤小鼠脾脏生发中心周围积聚的MDSCs与B细胞共定位。在MDSCs存在的情况下，小鼠对替代抗原的抗体反应显著增强，尤其是免疫球蛋白（Ig）A亚型。体外与MDSCs共培养促进了B细胞的增殖和分化，使其成为产生IgA的浆细胞。有趣的是，MDSCs与B细胞之间的相互作用需要细胞间接触。来自肿瘤坏死因子受体（TNFR）2小鼠而非TNFR1小鼠的MDSCs无法促进B细胞反应。进一步研究表明，白细胞介素-10和转化生长因子-β1对于MDSC介导的IgA反应促进至关重要。这些结果证明了肿瘤生长过程中MDSC介导的免疫调节的新机制。
