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).


CONCLUSIONS
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.
Steinmetz
Oliver M
OM
Medizinische Klinik IV, Universitätsklinikum Hamburg Eppendorf, Germany.
Panzer
Ulf
U
Kneissler
Ursula
U
Harendza
Sigrid
S
Lipp
Martin
M
Helmchen
Udo
U
Stahl
Rolf A K
RA
D000208:Acute Disease; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000235:genetics*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics*
C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D008562:Membrane Glycoproteins; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine