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Chemokine receptor expression and functional effects of chemokines on B cells: implication in the pathogenesis of rheumatoid arthritis
Arthritis Research & Therapy, 10/07/09

Nanki T et al. – The data suggest that CCR5, CCR6, CCR7, CXCR3, CXCR4 and CXCR5 may be important for the B cell migration into the synovium of RA patients, and also their local proliferation, cytokine production and ICOSL expression in the synovium.

• Cell surface molecule expression analyzed by flow cytometry
• Cellular migration assessed using chemotaxis chambers
• Cellular proliferation was examined by 3H-thymidine incorporation
• TNF production assayed by enzyme-linked immunosorbent assay

• Significant numbers of peripheral blood B cells of healthy donors and subjects with RA expressed CC chemokine receptor (CCR)5 and CXCR3, and most B cells expressed CCR6, CCR7, CXCR4 and CXCR5
• Synovial B cells more frequently expressed CCR5, but less often expressed CCR6, CCR7 and CXCR5 compared to peripheral blood in RA
• Further functional analyses performed on peripheral blood B cells from healthy donors
• Migration of peripheral blood B cells, especially CD27+ B cells, was enhanced by CC chemokine ligand (CCL)20, CCL19, CCL21 and CXCL12.
• All four chemokines alone induced B cell proliferation; with CCL21 being the most effective
• CCL21 also enhanced proliferation of anti-IgM-stimulated B cells and blockade of CCR7 inhibited this effect
• CCL20, CCL21 and CXCL12 enhanced TNF production by anti-IgM mAb-stimulated B cells
• Finally, stimulation with CXCL12, but not CCL20, CCL19 and CCL21, enhanced inducible costimulator-ligand (ICOSL) expression by peripheral blood B cells of healthy donors and RA, but did not increase B cell-activating factor receptor or transmembrane activator and CAML-interactor

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