title: Molecular case report: IgVH analysis in acute humoral and cellular liver allograft rejection suggests a selected accumulation of effector B cells and plasma cells.
abstract: Acute cellular (CLR) and humoral liver allograft rejection (HLR) are the most important immunological obstacles to successful liver transplantation. In HLR, serum antibodies play the central pathogenetic role. In CLR, CD3+ T lymphocytes drive the destructive immune response. Although CLR and HLR show different clinical symptoms and can be kept apart in most cases, they share histomorphological similarities. In CLR, hepatic B lymphocytes and plasma cells as well as B-cell-activating cytokines have recently been described, indicating that, in addition to T cells, antibody-mediated mechanisms might be involved. To analyze the impact of hepatic B cells in CLR and HLR, the immunoglobulin (Ig) variable (V)-region gene repertoire was determined from tissue of one case of CLR and one case of HLR. Complement deposits and lymphocytic infiltrate were determined using immunohistochemistry. T cells, B lymphocytes and plasma cells could be detected in both cases, whereas C3c and C4d deposits could only be demonstrated in the HLR case. The molecular analysis of 63 V-region genes showed that B cells in both allografts expressed selected V-gene repertoires. All sequences differed from the putative germline sequences by multiple somatic mutations. This suggests a clonal expansion of selected effector B cells in the portal tracts of liver allografts. Locally accumulated B cells and their antibodies might be involved in IgG-mediated complement activation in CLR and HLR.
authors.affiliation: Institute for Pathology, University Hospital Charite, Schumannstrasse 20/21, 10117 Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Moeller
authors.forename: Manfred G
authors.initials: MG
authors.lastname: Krukemeyer
authors.forename: Lars
authors.initials: L
authors.lastname: Morawietz
authors.forename: Max
authors.initials: M
authors.lastname: Schmeding
authors.forename: Anja
authors.initials: A
authors.lastname: Dankof
authors.forename: Ulf
authors.initials: U
authors.lastname: Neumann
authors.forename: Veit
authors.initials: V
authors.lastname: Krenn
authors.forename: Claudia
authors.initials: C
authors.lastname: Berek
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007150:Immunohistochemistry; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D007135:Immunoglobulin Variable Region