Single-cell RNA sequencing of B cells from healthy donors and SLE patients

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by pathogenic auto-antibodies that cause end organ damage. B cells are thought to play a central role in the immunopathogenesis of SLE and display several abnormalities in patients, including a strong type I interferon signature as well as lower expression of surface markers including TLR9 and Fc?RIIB. To characterize differences in the proportion of distinct B cell subsets as well as intrinsic transcriptomic differences between B cells from healthy donors and SLE patients, we performed single-cell RNA sequencing on B cells isolated from PBMCs of donors. Several notable features were observed, including a strong interferon response signature among SLE B cells, and the expansion of CD11c+T-bet+ B cell subsets in these patients. Additionally, several surface molecules including MHC Class II proteins and surface proteins such as CD74 and CD52 were found to be differentially expressed in B cells isolated from SLE patients. The differences in B cell subset proportion as well as expression of various genes might play a role in B cell mediated pathogenesis of SLE. Overall design: Whole transcriptome data for HC (n = 2) and SLE (n = 3).

系统性红斑狼疮（Systemic Lupus Erythematosus, SLE）是一类以致病性自身抗体介导终末器官损伤为特征的自身免疫性疾病。现有研究表明，B细胞在SLE的免疫发病机制中居于核心地位，患者体内的B细胞存在多项异常，包括显著的I型干扰素（type I interferon）应答特征，以及TLR9、FcγRIIB（FcγRIIB）等表面标志物的表达水平降低。为明确健康供者与SLE患者B细胞的亚群比例差异，以及不同来源B细胞的内在转录组特征差异，本研究对从供者外周血单个核细胞（Peripheral Blood Mononuclear Cells, PBMC）中分离得到的B细胞进行了单细胞RNA测序（single-cell RNA sequencing）。研究观察到多项标志性变化：SLE患者的B细胞中存在强烈的干扰素应答特征，且CD11c+T-bet+ B细胞亚群在该类患者体内发生扩增；此外，在SLE患者来源的B细胞中，包括MHC II类蛋白（MHC Class II proteins）以及CD74、CD52等在内的多种表面分子均呈现差异表达。B细胞亚群比例的改变与各类基因的表达差异，可能参与B细胞介导的SLE发病过程。总体实验设计：健康对照组（HC, n=2）与SLE组（n=3）的全转录组数据。