AbstractBackgroundLymphocyte activation gene-3 (LAG3) positive B cells have been identified as a novel regulatory B cell subset, while the role of LAG3+B cells in the pathogenesis of rheumatoid arthritis (RA) remains elusive.Materials and methodsPeripheral blood mononuclear cells (PBMCs) from RA, osteoarthritis (OA) patients and healthy volunteers were collected for flow cytometry staining of LAG3+B cells. Their correlation with RA patient clinical and immunological features were analyzed. Moreover, the frequencies of LAG3+B cells in collagen-induced arthritis (CIA) mice and naive mice were also detected.ResultsA significant decrease of LAG3+B cells was observed in RA patients as compared with healthy individuals and OA patients. Notably, the frequencies of LAG3+B cells were negatively correlated with tender joint count (r = −0.4301,p= .0157) and DAS28-ESR (r = −0.4018,p= .025) in RA patients. In CIA mice, LAG3+B cell frequencies were also decreased and negatively correlated with the CIA arthritis score.ConclusionsImpairment of LAG3+B cells potentially contributes to RA development. Reconstituting LAG3+B cells might provide novel therapeutic strategies for the persistent disease.Key messagesLAG3+B cells have been identified as a novel regulatory B cell subset. However, its role in the pathogenesis of RA remains unknown.This study revealed the decreased frequency of LAG3+B cells in RA patients. Notably, LAG3+B cells were negatively correlated with RA disease activity including the tender joint count and DAS28-ESR.In CIA mice, LAG3+B cell frequencies were also decreased and negatively correlated with the CIA arthritis score.Reconstitution of LAG3+B cells might provide novel therapeutic strategies for disease perpetuation.