Patients with systemic lupus erythematosus show increased proportions of CD19+CD20− B cells and secretion of related autoantibodies

Abstract

At present, anti-CD20 monoclonal antibody treatments targeting systemic lupus erythematosus (SLE) are complex, variable, and often have disappointing outcomes. High levels of programmed cell death-1 (PD-1) and its ligands (PD-L1, PD-L2) or CD80/CD86 on B cell surfaces are markers of increased B cell activity. However, their expression levels on CD19+CD20+/- B cells and their clinical significance for SLE dynamics have not been carefully investigated. Flow cytometry was used to detect the expression levels of PD-1, PD-L1, PD-L2, CD80, and CD86 on CD19+CD20+/- B cells in peripheral blood from SLE patients and healthy controls (HCs). The amount of anti-dsDNA and immunoglobin G (IgG) secreted by CD19+CD20+/- B cells was measured by enzyme-linked immunosorbent assay. CD19+CD20- B cell frequency was significantly higher in SLE patients than in HCs (P < 0.001), and was positively correlated with disease activity. In SLE patients, frequencies of PD-1, PD-L1, PD-L2, and CD86 on CD19+CD20- B cells were significantly higher than CD19+CD20+ B cells (P ≤ 0.002) and were significantly correlated with individual laboratory and clinically based parameters (P < 0.05). In vitro tests, we found that the levels of anti-dsDNA and IgG secreted by CD19+CD20- B cells from patients with SLE were significantly higher than the HC group (P < 0.05). We found abnormal frequency of CD19+CD20- B cells and increased expression of surface markers on these cells from SLE patients. And the CD19+CD20- B cells had the ability to proliferate and secrete anti-dsDNA and IgG. Additionally, our results suggested that CD19+CD20- B cells from SLE patients may be the activated B cells and caused poor efficacy of rituximab. Key Points • CD19+CD20- B cell frequencies were significantly higher in SLE patients. • Frequencies of PD-1 and its ligands on CD19+CD20- B cells increased significantly in SLE patients. • CD19+CD20- B cells in SLE patients had the ability to secrete anti-dsDNA and IgG. • CD19+CD20- B cells in SLE patients may be the activated B cells and caused poor efficacy of rituximab.