Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation.
Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation.
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DOI：
10.3389/fimmu.2015.00496
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发表时间：
2015
影响因子：
7.3
通讯作者：
Catalán D
中科院分区：
文献类型：
--
作者：
Soto L;Ferrier A;Aravena O;Fonseca E;Berendsen J;Biere A;Bueno D;Ramos V;Aguillón JC;Catalán D
B细胞的激活阈值受到一系列抑制和激活受体的严格调节，因此它们的表达受到干扰可导致自身免疫的出现。本研究的目的是评估系统性硬化症患者过渡性、初始性和记忆性B细胞亚群中参与B细胞功能调节的激活和抑制分子的表达。为此，研究人员从31名系统性硬化症患者和53名健康人身上抽取了血液样本。流式细胞术检测细胞表面CD86、MHCⅱ、CD19、CD21、CD40、CD22、Siglec 10、CD35和FcγRIIB的表达。分离的B细胞通过细胞内流式细胞术检测IL-10的产生。用ELISA法测定受刺激B细胞上清液中可溶性IL-6和IL-10的水平。与健康对照相比，系统性硬化症患者表现出与记忆B细胞相关的过渡性和幼稚B细胞的频率增加。与健康供者相比，患者的移行性和未成熟B细胞表达更高水平的CD86和FcγRIIB。此外，来自患者的B细胞表现出CD19和CD40的高表达，而来自系统性硬化症患者的记忆细胞则表现出CD35的低表达。CD19和CD35的表达水平与不同的自身抗体谱相关。患者IL-10+ B细胞及IL-10分泌水平均明显降低。总之，系统性硬化症患者表现出参与b细胞调节的分子表达的改变。这些异常可能是系统性硬化症中观察到的b细胞过度活化的决定性因素。
The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10+ B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis.