Differential expression of chemokine receptors on peripheral blood B cells from patients with rheumatoid arthritis and systemic lupus erythematosus

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.

Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic lupus erythematosus

“…In addition, CXCR4 surface expression reached different levels on total B cells (geometric mean fluorescence intensity (MFI) median value 55, range: 11 to 217) and the different B-cell subsets as well (Additional file 1: Figure S1A). In line with previous works [41], CXCR4 expression on circulating B cells was significantly lower in SLE patients than in healthy controls (Figures 3A and B and Additional file 1: Figure S1A). Because the decrease in CXCR4 expression could be due to changes in the proportion of B-cell subsets or variations in expression levels within subsets, we performed an intra-subset analysis.…”

“…Consistent with previous works [1,41], several abnormalities of the B-cell compartment were detected in the peripheral blood of SLE patients including a B-cell lymphopenia that predominantly affects naive B cells (Figure 1B and Table 1). In contrast, a significant increase in the frequency of PC was observed in patients with SLE (Figure 1A).…”

“…Thus, our findings provided evidence that SLE B cells display a loss of membrane CXCR4 expression. In agreement with this, Henneken and coworkers previously showed a decrease in CXCR4-positive naive and overall CD27 + B cells from 4 SLE patients [41]. Because CXCR4 is virtually expressed on all B-cell subsets, changes in CXCL12 responsiveness that occur throughout lymphocyte ontogeny were proposed to result from differences in the activation of CXCR4-mediated signaling [15].…”

Enhanced Activation of Memory, but Not Naïve, B Cells in Chronic Hepatitis C Virus-Infected Patients with Cryoglobulinemia and Advanced Liver Fibrosis

“…In addition, only naïve B cell CD183 expression levels negatively correlated with the percent cryocrit, which could indicate that naïve B cell migration is altered in those patients with the highest levels of cryoglobulins. Further work is needed to investigate the expression of other chemokine receptors such as CXCR5, which was shown to be negatively correlated with the expression of CD183 on rheumatoid arthritis patient’s B cells [30]. We also report for the first time that memory B cell CD86 expression levels and percentages of memory B cells expressing CD86 were significantly associated with advanced liver disease, whereas all other activation markers measured remained unchanged.…”

Impact of Therapy With Biological Agents on B-Lymphocyte Subpopulations in Rheumatic Diseases: New Evidence

“…Поликлональная активация В-клеток при ревматоидном артрите (РА) и системной красной волчанке (СКВ) сопровождается нарушением го-меостаза В-лимфоцитов периферической крови [7,8], в частности, выраженной экспансией CD27+ В-клеток памяти [9,10]. Полагают, что увеличение количества В-клеток памяти, отражающее потерю периферической то-лерантности, дефект негативной селекции, усиление ак-тивации и дифференцировки наивных В-клеток, а также отсутствие чувствительности к иммуносупрессивным препаратам, значительно повышает риск развития ауто-иммунных реакций [11].…”