Abstract

Chemokines and their receptors are essential in the recruitment and positioning of lymphocytes. To address the question of B cell migration into the inflamed synovial tissue of patients with rheumatoid arthritis (RA), peripheral blood naive B cells, memory B cells and plasma cells were analyzed for cell surface expression of the chemokine receptors CXCR3, CXCR4, CXCR5, CCR5, CCR6, CCR7 and CCR9. For comparison, B cells in the peripheral blood of patients with the autoimmune disease systemic lupus erythematosus (SLE) or with the degenerative disease osteoarthritis (OA) were analyzed. Expression levels of chemokine receptors were measured by flow cytometry and were compared between the different patient groups and healthy individuals. The analysis of chemokine receptor expression showed that the majority of peripheral blood B cells is positive for CXCR3, CXCR4, CXCR5, CCR6 and CCR7. Whereas a small fraction of B cells were positive for CCR5, practically no expression of CCR9 was found. In comparison with healthy individuals, in patients with RA a significant fraction of B cells showed a decreased expression of CXCR5 and CCR6 and increased levels of CXCR3. The downregulation of CXCR5 correlated with an upregulation of CXCR3. In patients with SLE, significant changes in CXCR5 expression were seen. The functionality of the chemokine receptors CXCR3 and CXCR4 was demonstrated by transmigration assays with the chemokines CXCL10 and CXCL12, respectively. Our results suggest that chronic inflammation leads to modulation of chemokine receptor expression on peripheral blood B cells. However, differences between patients with RA and patients with SLE point toward a disease-specific regulation of receptor expression. These differences may influence the migrational behavior of B cells.

Highlights

  • Rheumatoid arthritis (RA) is a complex autoimmune disease of unknown etiology

  • The cytometric analysis of healthy controls showed that 93.9% of the B cells were positive for CXCR3, 81.6% for CXCR4, 97.6% for CXCR5, 76.7% for CCR6 and 94.3% for CCR7

  • We found that in healthy individuals most B cells are positive for CXCR3; the mean fluorescence intensity was rather low and only a few B cells expressed CXCR3, at a level comparable to that seen after staining with mAb specific for CXCR5 (Figs 1 and 7)

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Summary

Introduction

Rheumatoid arthritis (RA) is a complex autoimmune disease of unknown etiology. It is characterized by chronic inflammation of the synovial membrane and the formation of a pannus, which leads to swollen joints and to joint destruction. Inflammatory cells such as monocytes and neutrophils, together with T and B cells, infiltrate the synovial membrane [1]. Migration of lymphocytes from the blood to the synovial tissue is a multi-step process controlled in part by interactions between chemokines and their receptors [2,3]. Cells of the lymphoid lineages dynamically change their expression profiles of chemokine receptors, which results in specific migration in response to chemokines [5,6]

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