Description of B lymphocytes and plasma cells, complement, and chemokines/receptors in acute liver allograft rejection.
BACKGROUND
Although antibody mechanisms play a pathogenetic role in liver allograft rejection, no data exist on B lymphocytes, plasma cells, complement, and chemokines in rejected liver tissue.


METHODS
Liver biopsy specimens from 25 patients with acute allograft rejection (AR) (rejection activity index, RAI score: 1-9) were analyzed by immunohistochemistry (IH) and reverse transcriptase-polymerase chain reaction (RT-PCR) and compared with biopsy specimens taken prior to implantation (PI). The number of CD20 and CD138 cells was evaluated, and the presence and abundance of the chemokines macrophage inflammatory protein (MIP)-3alpha, CXCL9, CXCL10, CXCL11, CXCL12, and their receptors CCR-6, CXCR3, and CXCR4 were examined. Complement depositions were visualized by C4d IH.


RESULTS
The numbers of B lymphocytes (P=0.002) and plasma cells (P=0.022) were significantly higher in AR biopsy specimens compared with PI biopsy specimens. MIP-3alpha and CCR-6 cells were detected in the portal fields of all AR biopsy specimens. IH double staining revealed a colocalization of MIP-3alpha/CD20 cells; C4d deposits could be demonstrated along the portal capillaries. All examined chemokines and receptors could be detected in normal liver tissue and in AR biopsy specimens by RT-PCR and semiquantitative RT-PCR, demonstrating an overexpression of CXCL10 and -11.


CONCLUSIONS
The significant increase of B lymphocytes and plasma cells during acute rejection, together with the lack of a significant increase of proliferating cells, indicates that the migration of B lymphocytes and plasma cells-promoted by the expression of B-cell activating chemokines/receptors-plays a key role in acute liver rejection. The C4d deposits along the portal capillaries indicate a humorally mediated alloresponse caused by the accumulated B and plasma cells.
Krukemeyer
Manfred G
MG
Institute of Pathology, Humboldt-University, University Hospital Charité, Berlin, Germany.
Moeller
Johannes
J
Morawietz
Lars
L
Rudolph
Birgit
B
Neumann
Ulf
U
Theruvath
Tom
T
Neuhaus
Peter
P
Krenn
Veit
V
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001706:Biopsy; D054418:Chemokine CCL20; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003181:Complement C4 / Q000276:immunology / Q000378:metabolism*; D015935:Complement C4b; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D053668:Syndecan-1; D053667:Syndecans; D014184:Transplantation, Homologous
D018951:Antigens, CD20; C108355:CCL20 protein, human; C106311:CCR6 protein, human; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C515255:CXCL12 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054418:Chemokine CCL20; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D019742:Chemokines, CC; D019743:Chemokines, CXC; D003181:Complement C4; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011509:Proteoglycans; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D015935:Complement C4b; C032261:complement C4d