AUTHOR=Daamen Andrea R. , Alajoleen Razan M. , Grammer Amrie C. , Luo Xin M. , Lipsky Peter E. 

TITLE=Single-cell RNA sequencing analysis reveals the heterogeneity of IL-10 producing regulatory B cells in lupus-prone mice

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1282770

DOI=10.3389/fimmu.2023.1282770

ISSN=1664-3224

ABSTRACT=Introduction: B cells can have both pathogenic and protective roles in autoimmune diseases, including systemic lupus erythematosus (SLE). Deficiencies in the number or immunosuppressive function of IL-10 producing regulatory B cells (Bregs) can cause exacerbated autoimmune inflammation. However, the exact role of Bregs in lupus pathogenesis has not been elucidated.We carried out gene expression analysis by scRNA-seq to characterize differences in splenic Breg subsets and molecular profiles through stages of disease progression in lupus-prone mice. Transcriptome-based changes in Bregs from mice with active disease were confirmed by phenotypic analysis.We found that a loss of marginal zone (MZ) lineage Bregs, an increase in plasmablast/plasma cell (PB-PC) lineage Bregs, and overall increases in inflammatory gene signatures were characteristic of active disease as compared to Bregs from the pre-disease stage. However, the frequencies of both MZ Bregs and PB-PCs expressing IL-10 were significantly decreased in active-disease mice.Conclusions: Overall, we have identified changes to the repertoire and transcriptional landscape of Breg subsets associated with active disease that provide insights into the role of Bregs in lupus 2 This is a provisional file, not the final typeset article pathogenesis. These results could inform the design of Breg-targeted therapies and interventions to restore Breg suppressive function in autoimmunity.