Description of B Lymphocytes and Plasma Cells, Complement, and Chemokines/Receptors in Acute Liver Allograft Rejection

Abstract

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. 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)-3α, CXCL9, CXCL10, CXCL11, CXCL12, and their receptors CCR-6, CXCR3, and CXCR4 were examined. Complement depositions were visualized by C4d IH. 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-3α+ and CCR-6+ cells were detected in the portal fields of all AR biopsy specimens. IH double staining revealed a colocalization of MIP-3α+/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. 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.