Renoprotective anti-CD45RB antibody induces B cell production in systemic lupus erythematosus based on single-cell RNA-seq analysis

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that commonly affects the kidney. Single-cell RNA sequencing (scRNA-seq) technology is a powerful tool for characterizing individual cells and elucidating biological mechanisms at the cellular level. The purpose of this study was to identify the mechanism underlying kidney injury in SLE using scRNA-seq technology. Methods: scRNA-seq data of peripheral blood mononuclear cells (PBMCs) in SLE were retrieved from the GEO database, followed by batch effect elimination, dimensionality reduction, cluster analysis, cell annotation and enrichment analysis. A model of SLE was developed in NZB/WF1 mice. Effects of anti-CD45RB antibody on the SLE-induced kidney injury were evaluated, and we measured the distribution of regulatory T cells and B cells in mouse spleen and kidney tissues, levels of kidney function-related indexes, deposition of IgG and C3 in the glomeruli, and the levels of inflammatory cytokines. CD45RB was a specific marker gene of B cell clusters and had influence on the B cells. anti-CD45RB antibody treatment induced regulatory B cells and consequently arrested the kidney injury caused by SLE. In addition, depletion of regulatory T cells was found to partially undermine the alleviatory effect of anti-CD45RB antibody on SLE-induced kidney injury. Collectively, our data suggest that anti-CD45RB antibody can prevent the SLE-induced kidney injury, pointing to anti-CD45RB antibody as a potential therapeutic strategy in kidney injury-related disease.