Single-Cell RNA Sequencing Reveals Disease Stage-Dependent Transcriptomic Profiles of Regulatory B Cells in Systemic Lupus Erythematosus

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease associated with abnormal activation of immune cells. Regulatory B (Breg) cells are a cell subset that negatively regulate responses via secretion immunoregulatory cytokines interleukin (IL)-10, IL-35, and transforming growth factor (TGF)-β. We had previously shown in lupus-prone MRL/lpr mice, pre-disease Breg were more potent suppressing autoimmunity than active-disease In this study, using single-cell RNA (scRNA) sequencing, we profiled ~10,000 from female mice at the (6–8 weeks age) vs. (10–12 stages. Based on known markers subsets, scRNA analysis identified respective clusters as transtional-2 marginal zone precursor (T2-MZP), (MZB), transitional 1 (T1), germinal center (GC), B1 Our data showed predominantly T2-MZP MZB Follicular outside zone, other hand, significantly increased stage. Two long noncoding RNAs (lncRNAs), Malat1 Xist, cells, where expression Lglas3, Slpi, Spp1 was also increased. Notably, exhibited exhausted phenotype T-bet (Tbx21). Collectively, our findings suggest SLE stage-dependent functions regulated transcriptional level. future experiments, will determine whether immunosuppressive can be restored by knocking down differentially overexpressed genes.