Lee D-S, Yi T G, Lee H-J, Kim S-N, Park S, Jeon M-S, Song S U
Department of Biomedical Sciences, Inha University School of Medicine, Incheon, Republic of Korea.
1] Translational Research Center, Inha University School of Medicine, Incheon, Republic of Korea [2] Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, Republic of Korea.
Cell Death Dis. 2014 Apr 24;5(4):e1192. doi: 10.1038/cddis.2014.147.
Mesenchymal stem cells (MSCs) have immunomodulatory functions such as the suppression of T and B cells. MSCs suppress immunoglobulin (Ig) production by B cells via cell-cell contact as well as via secretion of soluble factors. Our study showed that the conditioned medium (CM) of MSCs infected with a mycoplasma strain, Mycoplasma arginini, has marked inhibitory effects on Ig production by lipopolysaccharide/interleukin-4-induced B cells compared with mycoplasma-free MSC-CM. We analyzed mycoplasma-infected MSC-CM by fast protein liquid chromatography and liquid chromatography to screen the molecules responsible for Ig inhibition. Complement C3 (C3) was the most critical molecule among the candidates identified. C3 was shown to be involved in the suppression of the Ig production of B cells. C3 was secreted by mycoplasma-infected MSCs, but not by mycoplasma-free MSCs or B cells. It was able to directly inhibit Ig production by B cells. In the presence of a C3 inhibitor, Ig inhibition by MSC-CM was abrogated. This inhibitory effect was concomitant with the downregulation of B-cell-induced maturation protein-1, which is a regulator of the differentiation of antibody-secreting plasma cells. These results suggest that C3 secreted from mycoplasma-infected MSCs has an important role in the immunomodulatory functions of MSCs. However, its role in vivo needs to be explored.
间充质干细胞（MSCs）具有免疫调节功能，如抑制T细胞和B细胞。MSCs通过细胞间接触以及可溶性因子的分泌来抑制B细胞产生免疫球蛋白（Ig）。我们的研究表明，与无支原体的MSCs条件培养基（CM）相比，感染精氨酸支原体菌株的MSCs条件培养基对脂多糖/白细胞介素-4诱导的B细胞产生Ig具有显著的抑制作用。我们通过快速蛋白质液相色谱和液相色谱分析支原体感染的MSCs条件培养基，以筛选负责Ig抑制的分子。补体C3（C3）是所鉴定候选分子中最关键的分子。结果表明，C3参与了B细胞Ig产生的抑制。C3由支原体感染的MSCs分泌，但不由无支原体的MSCs或B细胞分泌。它能够直接抑制B细胞产生Ig。在存在C3抑制剂的情况下，MSCs条件培养基对Ig的抑制作用被消除。这种抑制作用与B细胞诱导的成熟蛋白-1的下调同时发生，B细胞诱导的成熟蛋白-1是抗体分泌浆细胞分化的调节因子。这些结果表明，支原体感染的MSCs分泌的C3在MSCs的免疫调节功能中具有重要作用。然而，其在体内的作用仍有待探索。
