Du H-Q, Zhang X, An Y-F, Ding Y, Zhao X-D
Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Division of Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Scand J Immunol. 2015 Jun;81(6):483-93. doi: 10.1111/sji.12282.
The Wiskott-Aldrich syndrome protein (WASp) is an important regulator of the actin cytoskeleton and is required for immune cell function. WASp deficiency causes a marked reduction in major mature peripheral B cell subsets, particularly marginal zone (MZ) B cells. We hypothesized that WASp deficiency may also lead to a reduction of regulatory B cells (known as B10 cells) belonging to a novel subset of B cells. And in consideration of the key role of B10 cells play in maintaining peripheral tolerance, we conjectured that a deficit of these cells could contribute to the autoimmunity in patients with Wiskott-Aldrich syndrome (WAS). The effects of WASp deficiency on B10 cells have been reported by only one group, which used an antigen-induced arthritis model. To add more information, we measured the percentage of B10 cells, regulatory T cells (Tregs) and Th1 cells in WASp knockout (WASp KO) mice. We also measured the percentage of B10 cells in patients with WAS by flow cytometry. Importantly, we used the non-induced autoimmune WASp KO mouse model to investigate the association between B10 cell frequency and the Treg/Th1 balance. We found that the percentage of B10 cells was reduced in both mice (steady state and inflammatory state) and in humans and that the lower B10 population correlated with an imbalance in the Treg/Th1 ratio in old WASp KO mice with autoimmune colitis. These findings suggest that WASp plays a crucial role in B10 cell development and that WASp-deficient B10 cells may contribute to autoimmunity in WAS.
威斯科特-奥尔德里奇综合征蛋白（WASp）是肌动蛋白细胞骨架的重要调节因子，是免疫细胞功能所必需的。WASp缺乏会导致主要成熟外周B细胞亚群显著减少，尤其是边缘区（MZ）B细胞。我们推测，WASp缺乏也可能导致属于新型B细胞亚群的调节性B细胞（称为B10细胞）减少。鉴于B10细胞在维持外周耐受性中发挥的关键作用，我们推测这些细胞的缺乏可能导致威斯科特-奥尔德里奇综合征（WAS）患者的自身免疫。关于WASp缺乏对B10细胞的影响，仅有一组报道，该组使用了抗原诱导的关节炎模型。为了补充更多信息，我们测量了WASp基因敲除（WASp KO）小鼠中B10细胞、调节性T细胞（Tregs）和Th1细胞的百分比。我们还通过流式细胞术测量了WAS患者中B10细胞的百分比。重要的是，我们使用非诱导性自身免疫WASp KO小鼠模型来研究B10细胞频率与Treg/Th1平衡之间的关联。我们发现，在小鼠（稳态和炎症状态）和人类中，B10细胞的百分比均降低，并且在患有自身免疫性结肠炎的老年WASp KO小鼠中，较低的B10细胞群体与Treg/Th1比值失衡相关。这些发现表明，WASp在B10细胞发育中起关键作用，并且WASp缺陷的B10细胞可能导致WAS中的自身免疫。
