CD52 Is Elevated on B cells of SLE Patients and Regulates B Cell Function.
CD52 Is Elevated on B cells of SLE Patients and Regulates B Cell Function.
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DOI：
10.3389/fimmu.2020.626820
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发表时间：
2020
影响因子：
7.3
通讯作者：
Robinson WH
中科院分区：
文献类型：
--
作者：
Bhamidipati K;Silberstein JL;Chaichian Y;Baker MC;Lanz TV;Zia A;Rasheed YS;Cochran JR;Robinson WH
系统性红斑狼疮（SLE）是一种自身免疫性疾病，以B细胞失调和耐受性中断为特征，导致致病性自身抗体的产生。我们对来自健康供体和SLE患者的B细胞进行了单细胞RNA测序，发现SLE患者中CD52表达上调。我们进一步证明SLE患者表现出显著增加的B细胞表面CD52表达水平和血浆可溶性CD52水平，可溶性CD52水平与狼疮疾病活动度呈正相关。使用CD52缺失的JeKo-1细胞，我们发现缺乏表面CD52表达的细胞对B细胞受体（BCR）信号反应过度，表明表面结合蛋白具有抑制作用。在健康的供体B细胞中，抗原特异性bcr激活以磷脂酶C依赖的方式启动CD52切割，显著降低细胞表面水平。重组CD52- fc的实验表明，可溶性CD52以部分依赖于siglece -10的方式抑制BCR信号。此外，用CD52-Fc孵育未受刺激的B细胞导致表面免疫球蛋白和CXCR5的减少。B细胞与CD52的长期孵育导致IgD+IgMlo无能B细胞的扩增。总之，我们的研究结果表明CD52在B细胞上作为一种稳态蛋白，通过抑制对BCR信号的反应而起作用。此外，我们的数据表明，CD52在抗原接合后从B细胞表面被切割，并能以自分泌和旁分泌的方式抑制B细胞的功能。我们认为SLE中B细胞CD52表达的增加代表了一种抑制B细胞过度活跃的稳态机制。
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell dysregulation and breaks in tolerance that lead to the production of pathogenic autoantibodies. We performed single-cell RNA sequencing of B cells from healthy donors and individuals with SLE which revealed upregulated CD52 expression in SLE patients. We further demonstrate that SLE patients exhibit significantly increased levels of B cell surface CD52 expression and plasma soluble CD52, and levels of soluble CD52 positively correlate with measures of lupus disease activity. Using CD52-deficient JeKo-1 cells, we show that cells lacking surface CD52 expression are hyperresponsive to B cell receptor (BCR) signaling, suggesting an inhibitory role for the surface-bound protein. In healthy donor B cells, antigen-specific BCR-activation initiated CD52 cleavage in a phospholipase C dependent manner, significantly reducing cell surface levels. Experiments with recombinant CD52-Fc showed that soluble CD52 inhibits BCR signaling in a manner partially-dependent on Siglec-10. Moreover, incubation of unstimulated B cells with CD52-Fc resulted in the reduction of surface immunoglobulin and CXCR5. Prolonged incubation of B cells with CD52 resulted in the expansion of IgD+IgMlo anergic B cells. In summary, our findings suggest that CD52 functions as a homeostatic protein on B cells, by inhibiting responses to BCR signaling. Further, our data demonstrate that CD52 is cleaved from the B cell surface upon antigen engagement, and can suppress B cell function in an autocrine and paracrine manner. We propose that increased expression of CD52 by B cells in SLE represents a homeostatic mechanism to suppress B cell hyperactivity.
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影响因子：
9.1
作者：
Chun, Hye-Young;Chung, Jae-Wook;Suh, Chang-Hee
通讯作者：
Suh, Chang-Hee
CD200，CD123，CD43和CD52的定量流式细胞仪评估是成熟B细胞肿瘤的鉴别诊断的工具。
影响因子：
--
作者：
Arlindo EM;Marcondes NA;Fernandes FB;Faulhaber GAM
通讯作者：
Faulhaber GAM
影响因子：
8
作者：
Gies, Vincent;Schickel, Jean-Nicolas;Korganow, Anne-Sophie
通讯作者：
Korganow, Anne-Sophie
影响因子：
--
作者：
HALE G;XIA M-Q;WALDMANN H
通讯作者：
WALDMANN H
DOI：
10.1126/science.1168988
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen GY;Tang J;Zheng P;Liu Y
通讯作者：
Liu Y