Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Clin Exp Rheumatol. 2019 Jul-Aug;37 Suppl 119(4):23-31. Epub 2019 Jan 17.
In systemic sclerosis (SSc), B cell hyperactivation and abnormality are considered to play an important role in the disease pathophysiology. We aimed to clarify if the abnormal activation of B cells involves inhibitory FcγRIIB on B cells in SSc patients.
Blood samples were collected from 76 SSc patients (38 limited cutaneous SSc and 38 diffuse cutaneous SSc) and 59 healthy controls. We evaluated the expression levels of FcγRIIB on different B cell subsets. B cells were classified into five subsets based on their surface phenotype as measured by flow cytometry: naïve B cells (CD19+IgD+CD27-), pre-switched memory B cells (CD19+IgD+CD27+), double-negative (DN) memory B cells (CD19+IgD-CD27-), switched memory B cells (CD19+IgD-CD27mid), and plasmablasts (CD19+IgD-CD27high). The expression levels of the activation markers CD80, CD86, and CD95 were also examined.
The expression levels of FcγRIIB on SSc naïve and DN memory B cells were significantly increased compared to healthy controls (p<0.05 and p<0.001, respectively). CD80, CD86, and CD95 expression levels were significantly higher in all five B cell subsets, except for CD80 in switched memory B cells and plasmablasts. Increased FcγRIIB expression levels on DN memory B cells were associated with disease activity as assessed by the European Scleroderma Study Group Activity Index, presence of interstitial lung disease (ILD), and reduced lung function. Intravenous cyclophosphamide pulse therapy decreased FcγRIIB expression levels on memory B cell subsets.
SSc B cells may exhibit compensatory elevation in the expression levels of FcγRIIB in order to suppress the abnormal activation of B cells. In addition, FcγRIIB expression levels may serve as a marker of severe complications, such as ILD, in SSc.
在系统性硬化症（SSc）中，B 细胞的过度激活和异常被认为在疾病发病机制中起重要作用。我们旨在阐明 SSc 患者 B 细胞的异常激活是否涉及 B 细胞上的抑制性 FcγRIIB。
采集了 76 例 SSc 患者（38 例局限性皮肤 SSc 和 38 例弥漫性皮肤 SSc）和 59 名健康对照者的血样。我们评估了 FcγRIIB 在不同 B 细胞亚群上的表达水平。通过流式细胞术测量 B 细胞的表面表型，将 B 细胞分为五个亚群：幼稚 B 细胞（CD19+IgD+CD27-）、前转换记忆 B 细胞（CD19+IgD+CD27+）、双阴性（DN）记忆 B 细胞（CD19+IgD-CD27-）、转换记忆 B 细胞（CD19+IgD-CD27mid）和浆母细胞（CD19+IgD-CD27high）。还检测了激活标志物 CD80、CD86 和 CD95 的表达水平。
与健康对照组相比，SSc 幼稚 B 细胞和 DN 记忆 B 细胞上 FcγRIIB 的表达水平显著升高（p<0.05 和 p<0.001）。除了转换记忆 B 细胞和浆母细胞中的 CD80 外，所有五个 B 细胞亚群的 CD80、CD86 和 CD95 的表达水平均显著升高。DN 记忆 B 细胞上增加的 FcγRIIB 表达水平与欧洲硬皮病研究组活动指数评估的疾病活动度、间质性肺病（ILD）的存在以及肺功能降低有关。静脉注射环磷酰胺脉冲治疗降低了记忆 B 细胞亚群上的 FcγRIIB 表达水平。
SSc B 细胞可能表现出 FcγRIIB 表达水平的代偿性升高，以抑制 B 细胞的异常激活。此外，FcγRIIB 表达水平可作为 SSc 严重并发症（如 ILD）的标志物。
