Liu Qun, Deng Yiyao, Liu Xiaomin, Zheng Ying, Li Qinggang, Cai Guangyan, Feng Zhe, Chen Xiangmei
School of Medicine, Nankai University, Tianjin, 300071, China.
Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, 100853, China.
Heliyon. 2023 Apr 23;9(5):e15684. doi: 10.1016/j.heliyon.2023.e15684. eCollection 2023 May.
Dysfunction of B-cell subsets is critical in the development of systemic lupus erythematosus (SLE). There is a great diversity of B-lineage cells, and their features and functions in SLE need to be clarified. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and bulk transcriptomic data of isolated B-cell subsets from patients with SLE and healthy controls (HCs). We preformed scRNA-seq analysis focused on the diversity of B-cell subsets and identified a subset of antigen-presenting B cells in SLE patients that highly expressed ITGAX. A list of marker genes of each B-cell subset in patients with SLE was also identified. Comparison of bulk transcriptomic data of isolated B-cell subpopulations between SLE patients and HCs revealed the upregulated differentially expressed genes (DEGs) for each B-cell subpopulation in SLE. Common genes identified using these two methods were considered to be upregulated marker genes of B cells in SLE. The scRNA-seq data of SLE patients and HCs revealed that CD70 and LY9 were overexpressed in B cells vs. other cell types from SLE patients, and this pattern was validated by RT‒qPCR. Because CD70 is the cellular ligand of CD27, previous studies on CD70 have focused mainly on T cells from SLE patients. LY9 appears to have different functions in mice and humans: its expression is decreased in lupus-prone mice but is increased in T cells and some B-cell subpopulations in SLE patients. Here, we describe the overexpression of two costimulatory molecules, CD70 and LY9, which may be a novel feature of B cells in SLE patients.
B细胞亚群功能障碍在系统性红斑狼疮（SLE）的发病过程中至关重要。B淋巴细胞谱系细胞具有高度多样性，其在SLE中的特征和功能有待阐明。在本研究中，我们分析了系统性红斑狼疮患者和健康对照（HC）外周血单个核细胞（PBMC）的单细胞RNA测序（scRNA-seq）数据以及分离出的B细胞亚群的批量转录组数据。我们进行了scRNA-seq分析，重点关注B细胞亚群的多样性，并在SLE患者中鉴定出一个高表达ITGAX的抗原呈递B细胞亚群。还确定了SLE患者中每个B细胞亚群的标记基因列表。比较SLE患者和HC之间分离出的B细胞亚群的批量转录组数据，揭示了SLE中每个B细胞亚群上调的差异表达基因（DEG）。使用这两种方法鉴定出的共同基因被认为是SLE中B细胞上调的标记基因。SLE患者和HC的scRNA-seq数据显示，与SLE患者的其他细胞类型相比，CD70和LY9在B细胞中过表达，这一模式通过RT-qPCR得到验证。由于CD70是CD27的细胞配体，之前关于CD70的研究主要集中在SLE患者的T细胞上。LY9在小鼠和人类中似乎具有不同的功能：其在狼疮易感小鼠中的表达降低，但在SLE患者的T细胞和一些B细胞亚群中增加。在这里，我们描述了两种共刺激分子CD70和LY9的过表达，这可能是SLE患者B细胞的一个新特征。
