PATTERNS OF EPSTEIN-BARR-VIRUS LATENT AND REPLICATIVE GENE-EXPRESSIONIN EPSTEIN-BARR-VIRUS B-CELL LYMPHOPROLIFERATIVE DISORDERS AFTER ORGAN-TRANSPLANTATION

B cell lymphoproliferative disorders arising in organ transplant recip ients (B cell posttransplant lymphoproliferative disorders [PTLD]) are generally associated with EBV. In previous reports, B cell PTLD were shown to express the full pattern of EBV latent genes, as in vitro-est ablished lymphoblastoid cell lines. Although viral linear DNA was dete cted in 40% of lymphoproliferative disorders from immunocompromised ho sts, immunophenotypic studies failed to detect late EBV replicative an tigens. The aim of this study was to investigate the relationship of E BV latent gene expression in B cell PTLD to morphology, clonality, and immunophenotype, and to examine the replicative state of EBV in malig nant cells. For this purpose, 9 cases of EBV-related B cell PTLD were analyzed. Immunoglobulin gene rearrangements were detected by Southern blot analysis. The presence of EBV was assessed by Southern blot and by in situ hybridization. B cell. differentiation antigens, adhesion a nd activation molecules, and EBV latent and replicative gene expressio n were studied using immunohistochemistry techniques. We demonstrated that EBV-related B cell PTLD exhibited varying patterns of latent vira l gene expression. Higher levels of adhesion molecules were detected i n latent membrane protein 1 (LMP1) or LMP1 plus EBV nuclear antigen 2 (EBNA2)-positive tumors than in LMP1 and EBNA2-negative tumors. In con trast, there was no relationship between CD21 and CD23 expression and latent EBV phenotype. Activation of the EBV replicative cycle was high lighted by BamHI Z left frame 1 expression in 5 of 9 cases. Less frequ ent expression of late viral proteins suggested that the initiation of the EBV lytic cycle might not always lead to virions production.