Experimental Therapeutics Laboratory, School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, SA, Australia.
Adelaide Medical School, Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
Front Immunol. 2019 Dec 11;10:2899. doi: 10.3389/fimmu.2019.02899. eCollection 2019.
A successful outcome to pregnancy is dependent on the ability of the maternal uterine microenvironment to regulate inflammation processes and establish maternal tolerance. Recently, B cells have been shown to influence pregnancy outcomes as aberrations in their numbers and functions are associated with obstetric complications. In this study, we aimed to comprehensively examine the population frequency and phenotypic profile of B cells over the course of murine pregnancy. Our results demonstrated a significant expansion in B cells within the uterus during the peri-implantation period, accompanied by alterations in B cell phenotype. Functional evaluation of uterine B cells purified from pregnant mice at day 5.5 post-coitus established their regulatory capacity as evidenced by effective suppression of proliferation and activation of syngeneic CD4 T cells. Flow cytometric analysis revealed that the uterine B cell population has an expanded pool of IL-10-producing B cells bearing upregulated expression of co-stimulatory molecules CD80 and CD86 and activation marker CD27. Our investigations herein demonstrate that during the critical stages surrounding implantation, uterine B cells are amplified and phenotypically modified to act in a regulatory manner that potentially contributes toward the establishment of maternal immunological tolerance in early pregnancy.
妊娠的成功结局取决于母体子宫微环境调节炎症过程和建立母体耐受的能力。最近,B 细胞已被证明会影响妊娠结局,因为其数量和功能的异常与产科并发症有关。在这项研究中,我们旨在全面检查小鼠妊娠过程中 B 细胞的群体频率和表型特征。我们的结果表明,在着床期,子宫内的 B 细胞显著扩增,同时 B 细胞表型发生改变。从交配后第 5.5 天的怀孕小鼠中纯化的子宫 B 细胞的功能评估证实了其调节能力,表现为有效抑制了同源 CD4 T 细胞的增殖和激活。流式细胞术分析显示,子宫 B 细胞群体中具有扩增的 IL-10 产生 B 细胞池,其共刺激分子 CD80 和 CD86 以及激活标志物 CD27 的表达上调。我们的研究表明,在围绕着床的关键阶段,子宫 B 细胞被扩增并表型修饰为调节方式,这可能有助于在早期妊娠中建立母体免疫耐受。