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Steinmetz, O.M. et al.

BCA-1/CXCL13 expression is associated with CXCR5-positive B-cell cluster formation in acute renal transplant rejection.

BACKGROUND: Recent studies showed a crucial role for B cells in acute renal allograft rejection. It remains largely unknown, however, which mechanisms lead to the B-cell recruitment into the allograft. The chemokine CXCL13 and its corresponding receptor CXCR5 play a central role in B-cell trafficking to secondary lymphatic tissue and ectopic B-cell clusters in rheumatoid arthritis. We therefore investigated the potential role of CXCL13 and CXCR5 in formation of B-cell clusters in renal transplant rejection. METHODS: Serial immunohistochemical staining for CXCL13, CXCR5, and CD20 was carried out in protocol biopsies of 23 patients obtained between day 4 and day 9 after renal transplantation. Intragraft mRNA expression of CXCL13 was assessed by real-time polymerase chain reaction (PCR) analysis. RESULTS: Of 23 kidney biopsies obtained between days 4 and 9 after renal transplantation, 13 revealed an acute rejection. Four of these patients showed a substantial infiltration of the transplant with cluster-forming B cells. By immunohistochemistry CXCL13 and the corresponding receptor CXCR5 were exclusively detected in areas of B-cell clusters. Intrarenal CXCL13 mRNA expression was 27-fold higher in transplants with B-cell clusters compared to rejecting allografts without B-cell accumulation (P= 0.011). CONCLUSION: We describe a striking colocalization of CXCL13 expression with CXCR5- and CD20-positive B cells in renal transplants undergoing rejection. This is the first study demonstrating a potential role of CXCL13 and its specific receptor CXCR5 in recruitment of B cells in renal allograft rejection.[1]

References

BCA-1/CXCL13 expression is associated with CXCR5-positive B-cell cluster formation in acute renal transplant rejection. Steinmetz, O.M., Panzer, U., Kneissler, U., Harendza, S., Lipp, M., Helmchen, U., Stahl, R.A. Kidney Int. (2005) [Pubmed]

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