Deep Phenotyping of CD11c(+) B Cells in Systemic Autoimmunity and Controls.
Deep Phenotyping of CD11c(+) B Cells in Systemic Autoimmunity and Controls.
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DOI：
10.3389/fimmu.2021.635615
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发表时间：
2021
影响因子：
7.3
通讯作者：
Dörner T
中科院分区：
文献类型：
--
作者：
Rincon-Arevalo H;Wiedemann A;Stefanski AL;Lettau M;Szelinski F;Fuchs S;Frei AP;Steinberg M;Kam-Thong T;Hatje K;Keller B;Warnatz K;Radbruch A;Lino AC;Schrezenmeier E;Dörner T
循环中的CD 11 c + B细胞是某些类型的自身免疫中的关键现象，但也在常规免疫应答的背景下进行了描述（即，感染、疫苗接种）。使用质谱仪分析单个免疫细胞上的46种不同标记物，我们系统地初步证实了系统性红斑狼疮（SLE）患者血液中CD 11 c + B细胞增加的存在。值得注意的是，CD 11 c −和CD 11 c + B细胞之间CD 21、CD 27和CD 38表达的显著差异变得明显。我们观察到CD 21 − CD 27 − B细胞和CD 21 − CD 38 − B细胞与CD 11 c + B细胞频率的直接相关性，与原发性干燥综合征患者（pSS）和健康供体（HD）相比，SLE患者中CD 21 − CD 27 − B细胞和CD 11 c + B细胞的频率最明显。因此，CD 11 c + B细胞主要存在于记忆亚群中，并富含CD 27 −IgD−、CD 21 − CD 27 −和CD 21 − CD 38 − B细胞表型。来自所有供体组（SLE、pSS和HD）的CD 11 c + B细胞显示出增强的CD 69、Ki-67、CD 45 RO、CD 45 RA和CD 19表达，而CXCR 5和CD 21的膜表达减少。值得注意的是，与HD相比，SLE CD 11 c + B细胞显示检查点分子CD 86、PD 1、PDL 1、CD 137、VISTA和CTLA-4的表达增强。CD 11 c + B细胞与CD 21 −表型共表达不同的活化和检查点标志物的显著增加，表明交替（滤泡外）B细胞活化途径的定量增加，可能与SLE显著炎症条件下观察到的异常免疫调节相关，表现出特征性PD-1/PD-L1上调。
Circulating CD11c+ B cells are a key phenomenon in certain types of autoimmunity but have also been described in the context of regular immune responses (i.e., infections, vaccination). Using mass cytometry to profile 46 different markers on individual immune cells, we systematically initially confirmed the presence of increased CD11c+ B cells in the blood of systemic lupus erythematosus (SLE) patients. Notably, significant differences in the expression of CD21, CD27, and CD38 became apparent between CD11c− and CD11c+ B cells. We observed direct correlation of the frequency of CD21−CD27− B cells and CD21−CD38− B cells with CD11c+ B cells, which were most pronounced in SLE compared to primary Sjögren's syndrome patients (pSS) and healthy donors (HD). Thus, CD11c+ B cells resided mainly within memory subsets and were enriched in CD27−IgD−, CD21−CD27−, and CD21−CD38− B cell phenotypes. CD11c+ B cells from all donor groups (SLE, pSS, and HD) showed enhanced CD69, Ki-67, CD45RO, CD45RA, and CD19 expression, whereas the membrane expression of CXCR5 and CD21 were diminished. Notably, SLE CD11c+ B cells showed enhanced expression of the checkpoint molecules CD86, PD1, PDL1, CD137, VISTA, and CTLA-4 compared to HD. The substantial increase of CD11c+ B cells with a CD21− phenotype co-expressing distinct activation and checkpoint markers, points to a quantitative increased alternate (extrafollicular) B cell activation route possibly related to abnormal immune regulation as seen under the striking inflammatory conditions of SLE which shows a characteristic PD-1/PD-L1 upregulation.
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影响因子：
6.2
作者：
Rose T;Szelinski F;Lisney A;Reiter K;Fleischer SJ;Burmester GR;Radbruch A;Hiepe F;Grützkau A;Biesen R;Dörner T
通讯作者：
Dörner T
影响因子：
3.8
作者：
Lu, Jen-Tang;Lu, Chien-Hung;Fleischer, Jason W.
通讯作者：
Fleischer, Jason W.
影响因子：
8.6
作者：
Doi, Hiroyoshi;Tanoue, Shiroh;Kaplan, David E.
通讯作者：
Kaplan, David E.
影响因子：
4.4
作者：
Fraussen, Judith;Marquez, Susanna;Somers, Veerle
通讯作者：
Somers, Veerle
影响因子：
32.4
作者：
Jenks SA;Cashman KS;Zumaquero E;Marigorta UM;Patel AV;Wang X;Tomar D;Woodruff MC;Simon Z;Bugrovsky R;Blalock EL;Scharer CD;Tipton CM;Wei C;Lim SS;Petri M;Niewold TB;Anolik JH;Gibson G;Lee FE;Boss JM;Lund FE;Sanz I
通讯作者：
Sanz I