A novel phenotype of B cells associated with enhanced phagocytic capability and chemotactic function after ischemic stroke.
A novel phenotype of B cells associated with enhanced phagocytic capability and chemotactic function after ischemic stroke.
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缺血性脑卒中后与增强的吞噬能力和趋化功能相关的B细胞新表型。
DOI：
10.4103/1673-5374.371365
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发表时间：
2023-11
影响因子：
6.1
通讯作者：
Shi L
中科院分区：
文献类型：
--
作者：
Wang R;Li H;Ling C;Zhang X;Lu J;Luan W;Zhang J;Shi L
越来越多的证据表明B细胞参与神经炎症和神经再生。然而，B细胞在缺血性卒中中的作用仍不清楚。在这项研究中，我们确定了一种新的表型的巨噬细胞样B细胞的脑浸润免疫细胞表达高水平的CD 45。巨噬细胞样B细胞以B细胞和巨噬细胞标志物的共表达为特征，与其他B细胞相比显示出更强的吞噬和趋化功能，并且显示出吞噬相关基因的上调表达。基因本体分析发现，与吞噬作用相关的基因，包括吞噬体和溶酶体相关基因的表达，在巨噬细胞样B细胞中上调。通过免疫染色和三维重建证实巨噬细胞样B细胞的吞噬活性，其中TREM 2标记的巨噬细胞样B细胞在脑缺血后吞噬并内化髓鞘碎片。细胞-细胞相互作用分析显示，巨噬细胞样B细胞主要通过CCL途径释放多种趋化因子来募集外周免疫细胞。单细胞RNA测序显示，向巨噬细胞样B细胞的转分化可以通过特异性上调转录因子CEBP家族向髓系和/或下调转录因子Pax 5向淋巴系诱导。此外，这种独特的B细胞表型在小鼠或创伤性脑损伤、阿尔茨海默病和胶质母细胞瘤患者的脑组织中检测到。总的来说，这些结果提供了一个新的视角，在缺血性脑B细胞的吞噬能力和趋化功能。这些细胞可能作为免疫调节靶点调节缺血性卒中的免疫应答。
Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration. However, the role of B cells in ischemic stroke remains unclear. In this study, we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45. Macrophage-like B cells characterized by co-expression of B-cell and macrophage markers, showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes. Gene Ontology analysis found that the expression of genes associated with phagocytosis, including phagosome- and lysosome-related genes, was upregulated in macrophage-like B cells. The phagocytic activity of macrophage-like B cells was verified by immunostaining and three-dimensional reconstruction, in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia. Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways. Single-cell RNA sequencing showed that the transdifferentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP family to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage. Furthermore, this distinct B cell phenotype was detected in brain tissues from mice or patients with traumatic brain injury, Alzheimer’s disease, and glioblastoma. Overall, these results provide a new perspective on the phagocytic capability and chemotactic function of B cells in the ischemic brain. These cells may serve as an immunotherapeutic target for regulating the immune response of ischemic stroke.
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影响因子：
4.4
作者：
CHEN, JZ;TROUNSTINE, M;HUSZAR, D
通讯作者：
HUSZAR, D
影响因子：
9.3
作者：
Eltayeb S;Berg AL;Lassmann H;Wallström E;Nilsson M;Olsson T;Ericsson-Dahlstrand A;Sunnemark D
通讯作者：
Sunnemark D
DOI：
10.1083/jcb.201004096
发表时间：
2010-06-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Elliott MR;Ravichandran KS
通讯作者：
Ravichandran KS
影响因子：
48
作者：
Aibar, Sara;Gonzalez-Blas, Carmen Bravo;Aerts, Stein
通讯作者：
Aerts, Stein
影响因子：
15.1
作者：
Cisbani, Giulia;Le Behot, Audrey;Rivest, Serge
通讯作者：
Rivest, Serge