Diminished LAG3+ B cells correlate with exacerbated rheumatoid arthritis

Abstract

Background: Lymphocyte 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 methods: Peripheral 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. Results: A 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. Conclusions: Impairment of LAG3+ B cells potentially contributes to RA development. Reconstituting LAG3+ B cells might provide novel therapeutic strategies for the persistent disease.Key messages LAG3+ 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.