Esteve-Solé Ana, Teixidó Irene, Deyà-Martínez Angela, Yagüe Jordi, Plaza-Martín Ana M, Juan Manel, Alsina Laia
Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Esplugues de Llobregat, Spain; Functional Unit of Clinical Immunology, Sant Joan de Déu-Hospital Clinic, Barcelona, Spain.
Materno-Fetal Medicine Department Hospital Clínic de Barcelona (HCB) , Barcelona , Spain.
Front Immunol. 2017 Mar 7;8:201. doi: 10.3389/fimmu.2017.00201. eCollection 2017.
The newborn's immune system must transition from a sterile haploidentical uterus to the world full of antigens. Regulatory B-cells (Breg; broadly defined as CD19CD24CD38) are tolerance promoters in the adult immune system. They can inhibit IFN-γ and IL-17 production by T-cells and are essential in different conditions, including pregnancy. Breg have still not been well characterized in umbilical cord blood, where we hypothesize that they are pivotal in the achievement of tolerance. We studied CD19CD24CD38 Breg in healthy umbilical cord blood (hUCB) compared to healthy peripheral adult blood (hAPB). Total numbers of Breg were increased in hUCB compared to hAPB (34.39 vs. 9.49%; = 0.0002), especially in the marginal zone-like B-cell subset, in which the most marked difference could be observed between hUCB and hAPB (60.80 vs. 4.94%; = 0.1). CD24CD38 subset in hUCB produced IL-10 and inhibited T-cell IFN-γ [1.63 vs. 0.95 stimulation ratio (SR); = 0.004] and IL-4 (1.63 vs. 1.44 SR; = 0.39) production. Phenotypically, hUCB Breg cells presented IgMIgDCD5CD10CD27 markers, similar to those described in hAPB Breg cells, but they showed increased IgM concentration and decreased expression of CD22 and CD73 markers. Our work characterized the frequency, phenotype, and function of Breg in hUCB, which may contribute to understanding of immune tolerance during pregnancy, paving the way to a new approach to immune-related diseases in the fetus and the newborn.
新生儿的免疫系统必须从无菌的半同基因子宫过渡到充满抗原的外部世界。调节性B细胞(Breg;广义定义为CD19⁺CD24⁺CD38⁺)是成人免疫系统中的耐受性促进因子。它们可以抑制T细胞产生干扰素-γ(IFN-γ)和白细胞介素-17(IL-17),并且在包括妊娠在内的不同情况下都至关重要。Breg在脐带血中的特征仍未得到充分研究,我们推测它们在实现耐受性方面起着关键作用。我们研究了健康脐带血(hUCB)与健康成人外周血(hAPB)中的CD19⁺CD24⁺CD38⁺ Breg。与hAPB相比,hUCB中Breg的总数增加(34.39%对9.49%;P = 0.0002),特别是在边缘区样B细胞亚群中,hUCB和hAPB之间观察到最显著的差异(60.80%对4.94%;P = 0.001)。hUCB中的CD24⁺CD38⁺亚群产生白细胞介素-10(IL-10)并抑制T细胞产生IFN-γ [刺激比(SR)为1.63对0.95;P = 0.004] 和IL-4(SR为1.63对1.44;P = 0.39)。在表型上,hUCB Breg细胞呈现IgM⁺IgD⁺CD5⁺CD10⁺CD27⁺标记,与hAPB Breg细胞中描述的标记相似,但它们显示出IgM浓度增加以及CD22和CD73标记的表达降低。我们的研究确定了hUCB中Breg的频率、表型和功能,这可能有助于理解妊娠期间的免疫耐受性,为胎儿和新生儿免疫相关疾病的新方法铺平道路。