Genetic Regulation of Exhausted and Classic Memory B Cells in Lupus Nephritis: Results from In Vitro Studies and Bioinformatic Analyses

Background: Disturbances in exhausted and classical memory B cells are crucial B lymphocyte abnormalities. Genetic dysregulation of exhausted and memory B cells in lupus nephritis remains unclear. Methods: We analyzed the single cell RNA-seq data of peripheral mononuclear blood cells from the NIH LN dataset (GSE135779) and another published LN single-cell RNA-seq dataset(dbGAP database accession code phs001457.v1.p1). Overlapping differentially expressed genes in exhausted and classical memory B cells from SLE and LN patients were identified, and their expression was validated in B cells obtained from LN patients and healthy controls. GO and KEGG analyses were used to analyze associated pathways. The circulating immune cells in SLE patients were analyzed and their relationship with candidate genes were examined. Results: IFI44L, XAF1, and MX1 were detected in both exhausted and classical memory B cells, and their increased expression were verified in classical and exhausted memory B cells were obtained from LN patients during remission. Protein protein interaction network of DEGs suggested that STAT1 showed the highest eigenvector centrality. GO and KEGG analyses also suggested that IFI44L, XAF1 and MX1 were involved in distinct biological processes and immune pathways related to SLE and LN. Circulating immune cell analysis revealed significant links between exhausted B cell, neutrophil, and immature B cell. Conclusion: Altered IFI44L, XAF1 and MX1 expression in exhausted and classical memory B cells may be related to the pathogenesis of SLE and LN. Funding: Government Support – Non-U.S.