Overexpression of CXCR4 on circulating B cells in patients with active systemic lupus erythematosus

Objective: To evaluate the roles of circulating B cells in the pathogenic process of systemic lupus erythematosus (SLE) by measuring the expression of chemokines and their receptors. Methods: Peripheral-blood mononuclear cells were obtained from 17 active, 21 inactive SLE patients, and 13 healthy controls. The expression of CXCR4, CXCR5, and CCR7 on CD19+ B cells was determined by flow cytometry, serum concentration of CXCL12 was measured by enzyme-linked immunosorbent assay, and the chemotactic responsiveness of B cells toward CXCL12 was evaluated. B or plasma cells expressing CXCR4 in renal biopsy specimens were detected using immnofluorescent staining. Results: Flow cytometric analysis revealed that expression level of CXCR4 on circulating B cells was significantly higher in patients with active disease than in those with inactive disease or controls. Serum CXCL12 concentration was not different between these groups. In addition, the migratory ability of B cells toward CXCL12 was enhanced in active SLE patients. Finally, CXCR4-expressing B cells were more frequently observed in the renal biopsy specimens of lupus nephritis. Conclusion: Up-regulated CXCR4 expression on circulating B cells in active SLE may enhance their chemotactic response toward CXCL12, which may promote infiltration of these cells into inflamed renal tissue and contribute to the development of SLE.