School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
Am J Reprod Immunol. 2019 Dec;82(6):e13187. doi: 10.1111/aji.13187. Epub 2019 Oct 6.
A successful outcome to pregnancy is critically dependent on the initiation of maternal immune tolerance before embryo implantation. Cells of embryonic origin that come in contact with the uterine microenvironment can exert influence over the phenotype and function of immune cells to facilitate robust implantation; however, what influence they may have on B cells remains unknown. In this study, we investigate the effect of human trophoblast cells on B-cell phenotype and the subsequent effect on peri-implantation events.
We cultured purified human B cells with the first-trimester human trophoblast cell line Swan 71 to investigate trophoblast-B-cell interactions and utilized trophoblast spheroids in an in vitro implantation model of migration and invasion.
Trophoblast-educated B cells or TE-B cells were found to consist of B cells in committed lineages such as plasmablasts and memory B cells, as well as increased proportions in subsets of CD24 CD27 regulatory B cells and CD19 IL-10 B cells. Conditioned media from the TE-B cells showed reduced production of pro-inflammatory cytokines that influenced the T-cell proliferation and cytokine production. Using trophoblast spheroids, we assessed the role of TE-B cells in trophoblast invasion and migration. Our results demonstrate a protective effect of TE-B-conditioned media against deleterious inflammation as evidenced by survival of the trophoblast spheroid in the presence of an immune assault and promotion of a migratory phenotype.
We posit that trophoblast-mediated education of B cells leads to their acquisition of properties capable of modulating inflammation in the uterine environment during the peri-implantation period.
妊娠的成功结局极大地依赖于胚胎着床前母体免疫耐受的启动。与子宫微环境接触的胚胎源性细胞可以影响免疫细胞的表型和功能，以促进胚胎的稳定着床；然而，它们对 B 细胞可能有何影响尚不清楚。在这项研究中，我们研究了人滋养层细胞对 B 细胞表型的影响，以及随后对着床前事件的影响。
我们培养纯化的人 B 细胞与第一孕期人滋养层细胞系 Swan 71 接触，以研究滋养层与 B 细胞的相互作用，并利用滋养层球体在体外迁移和侵袭的着床模型中进行研究。
发现滋养层教育的 B 细胞或 TE-B 细胞由浆母细胞和记忆 B 细胞等已定向分化的 B 细胞组成，以及 CD24 CD27 调节性 B 细胞和 CD19 IL-10 B 细胞亚群中的比例增加。TE-B 细胞的条件培养基显示促炎细胞因子的产生减少，这影响了 T 细胞的增殖和细胞因子的产生。使用滋养层球体，我们评估了 TE-B 细胞在滋养层侵袭和迁移中的作用。我们的结果表明，TE-B 条件培养基具有保护作用，可以防止有害炎症，因为在免疫攻击存在的情况下，滋养层球体得以存活，并促进迁移表型。
我们假设，滋养层介导的 B 细胞教育导致其获得在着床前期间调节子宫环境中炎症的能力。
