目的：探讨荷乳腺癌小鼠髓源抑制性细胞（myeloid-derived suppressor cell，MDSC）对B细胞功能的影响。方法：构建BABL/c 小鼠4T1 乳腺癌模型，磁珠分选出荷瘤小鼠脾脏的MDSC与正常小鼠脾脏的B细胞，将MDSC与B细胞共孵育后流式细胞术检测MDSC对B细胞表面分子PD-1、PD-L1、CTLA-4、CCR6、CD62L 和MHCⅡ表达的影响，ELISA 法检测B细胞分泌的IgA、IgM和IgG的变化；BrdU试剂盒检测B细胞增殖情况；Annexin Ⅴ/PI 凋亡试剂盒检测B细胞凋亡。磁珠分选出共孵育体系中的B细胞，将其与T细胞共孵育，BrdU 试剂盒检测T细胞增殖情况，Annexin Ⅴ/PI 凋亡试剂盒检测T细胞凋亡。结果：与B细胞对照组相比，B+MDSC组中B细胞表面PD-L1 表达升高（P<0.01），PD-1、CTLA-4、CCR6、CD62L 和MHCⅡ的表达均降低(均P<0.01)；B细胞分泌的IgA、IgM 和IgG 明显升高（均P<0.01），B细胞增殖增高（P<0.01）、凋亡降低（P<0.01）。与T细胞对照组相比，B+MDSC (1∶5）+T组的T细胞增殖明显降低（P<0.01），T细胞凋亡无明显变化。结论：荷乳腺癌小鼠MDSC促进B细胞增殖和抑制B细胞凋亡，并且MDSC诱导的B细胞可以抑制T细胞的增殖。

Objective: To investigate the effect of myeloid-derived suppressor cells (MDSCs) from mice bearing breast cancer on the function of normal B cells. Methods: A BABL/c mouse 4T1 breast cancer model was established. The spleen MDSCs of tumor-bearing mouse and normal mouse spleen B cells were sorted by magnetic beads, and the sorted MDSCs and B cells were co-incubated. Flow cytometry was used to test the effect of MDSCs on the expressions of B cell surface molecules, including PD-1, PD-L1, CTLA-4, CCR6,CD62L and MHCⅡ; ELISA assay was used to detect the secretion of IgA, IgM and IgG by B cells; BrdU kit was used to detect B cell proliferation; and Annexin V/PI staining was used to detect B cell apoptosis. B cells in the co-culture system were again sorted by magnetic beads and were then co-cultured with T cells; BrdU kit was used to detect T cell proliferation, and Annexin V/PI was used to detect T cell apoptosis. Results: Compared with B cell control group, the expression of PD-L1 on B cells in B+MDSC group was increased (P<0.01), while the expressions of PD-1, CTLA-4, CCR6, CD62L and MHC Ⅱ were all decreased (all P<0.01); The IgA, IgM and IgG secreted by B cells were significantly increased (all P<0.01); the proliferation of B cells was increased (P<0.01) and the apoptosis was decreased (P<0.01). Compared with the T cell control group, the proliferation of T cells in the B+MDSC (1:5) +T group was significantly reduced (P<0.01); however, there was no significant difference in T cell apoptosis. Conclusion: MDSCs from breast cancer bearing mice promotes B cell proliferation and inhibits B cell apoptosis, and the MDSC-induced B cells can inhibit T cell proliferation.

国家自然科学基金资助项目（No.81472471）