Diminished LAG3+ B cells correlate with exacerbated rheumatoid arthritis

Abstract

Abstract Background Regulatory B (Breg) cells negatively regulate immunity, and the impairment of Breg cells participates in the pathogenesis of rheumatoid arthritis (RA). Lymphocyte activation gene-3 (LAG3) is an inhibitory receptor involved in maintaining immune tolerance. LAG3+ B cells have been identified as a novel regulatory B cell subset. Nevertheless, its role in RA remains elusive. Methods Peripheral blood mononuclear cells (PBMCs) from RA, osteoarthritis (OA) patients and healthy volunteers were collected for flow cytometry staining of LAG3+ cells in different B cell subsets. Their frequencies with the clinical features and immunological characteristics of the RA patients were then analyzed. Moreover, collagen-induced arthritis (CIA) mouse models were also established for the detection of LAG3 + B cells and their potential involvement in the disease. Results A significant downregulation of LAG3+ B cells was observed in RA lymphocytes as well as B cell subsets 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 = 0.0157) and DAS28-ESR (r = -0.4018, p = 0.025) in RA patients. In CIA mouse models, LAG3+ B cell frequencies in LAG3+ CD86+ B cells, LAG3+ CD80+ B cells, LAG3+ CD69+ B cells and LAG3+ plasma B cells were also decreased, negatively correlating with the CIA arthritis score. Conclusions Impairment of LAG3+ B cells potentially contribute to the initiation and development of RA. Reconstituting LAG3+ B cells might provide novel therapeutic strategies for the persistent disease.