The Regulatory B Cell Compartment Expands Transiently During Childhood and Is Contracted in Children With Autoimmunity.

The Regulatory B Cell Compartment Expands Transiently During Childhood and Is Contracted in Children With Autoimmunity.
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DOI:
10.1002/art.39820
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发表时间:
2017-01
影响因子:
13.3
通讯作者:
Tedder, Thomas F.
Tedder, Thomas F.
中科院分区:
医学1区
文献类型:
--
作者:
Kalampokis, Ioannis;Venturi, Guglielmo M.;Poe, Jonathan C.;Dvergsten, Jeffrey A.;Sleasman, John W.;Tedder, Thomas F.

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通过白细胞介素-10(IL-10)分泌抑制免疫应答的调节性B细胞(B10细胞)已在患有自身免疫性疾病的成人中得到表征。这项研究检查了正常人类发育的整个年龄范围内的B10细胞,以及它们在儿科自身免疫过程中的变化。应用流式细胞仪检测了正常人和自身免疫性疾病患儿外周血B10细胞的表型和数量。通过测量B细胞衍生的IL-10对CD 4 + T细胞干扰素-γ(IFN-γ)表达的影响来评估B10细胞功能。酶联免疫吸附试验(ELISA)测定血清细胞因子水平。当高达30%的B细胞有能力产生IL-10时,B10细胞频率在儿童期短暂增加,而健康新生儿(3-4%)和成人(7-%)的频率较低。儿童B10细胞的表面表型显示出年龄依赖性变异。来自儿童的B10细胞不同于促炎性产生IFN-γ的B细胞,并且在体外下调CD 4 + T细胞IFN-γ的产生。与年龄匹配的健康对照组相比,自身免疫儿童的B10细胞频率和数量较低(分别下降39%和48%),IFN-γ较高,白细胞介素-21(IL-21)血清水平较低。体外实验中,IFN-γ抑制B细胞IL-10活性,而IL-21促进B细胞IL-10活性。B10细胞是一个功能明确的亚群,具有反映整体B细胞发育的可变表面表型,在儿童期短暂扩增。自身免疫性儿童B10细胞频率和数量的减少可能部分由IFN-γ和IL-21对B10细胞发育的差异调节以及血清细胞因子水平的改变来解释。
Regulatory B cells that inhibit immune responses through interleukin-10 (IL-10) secretion (B10 cells) have been characterized in adults with autoimmune disease. This study examines B10 cells across the entire age range of normal human development, and their changes during pediatric autoimmunity. The phenotype and numbers of blood B10 cells were examined in healthy individuals and children with autoimmunity by flow cytometry. B10 cell function was assessed by measuring the effect of B cell-derived IL-10 on CD4+ T cell interferon-gamma (IFN-γ) expression. Serum cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). B10 cell frequencies transiently increase during childhood when up to 30% of B cells were competent to produce IL-10, compared to the low frequencies in healthy newborns (3–4%) and adults (7–%). The surface phenotype of B10 cells in children revealed age-dependent variability. B10 cells from children were distinct from proinflammatory cytokine-producing B cells and down-regulated CD4+ T cell IFN-γ production in vitro. Compared to age-matched healthy controls, children with autoimmunity had lower B10 cell frequencies and numbers (decreased by 39% and 48%, respectively), higher IFN-γ and lower interleukin-21 (IL-21) serum levels. IFN-γ inhibited whereas IL-21 promoted B cell IL-10 competence in vitro. B10 cells, a functionally-defined subset with variable surface phenotype reflective of overall B cell development, transiently expand during childhood. The decreased B10 cell frequencies and numbers in children with autoimmunity may be partially explained by the differential regulation of B10 cell development by IFN-γ and IL-21 and alterations in serum cytokine levels.
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