Clonal analysis of transplant-associated lymphoproliferations based on the structure of the genomic termini of the Epstein-Barr virus

The clonal composition of various transplant-associated lymphoproliferations was assessed by means of Southern blot hybridizations using a DNA probe specific for the fused termini of the Epstein-Barr virus (EBV) genome. A single clonal band representing the joined EBV genomic termini was detected in most biopsies, demonstrating the presence of a monoclonal expansion of B lymphocytes carrying EBV DNA. Different configurations of immunoglobulin gene rearrangements and fused EBV genomic termini were frequently observed in tissues from different biopsy sites in individual patients, confirming the multiclonal origins for these lymphomas. In rare specimens, multiple forms of the joined termini were detected within individual lesions, which appeared polymorphous by histologic methods of analysis and polyclonal by immunologic and immunogenetic methods of analysis. These studies confirm that there is a spectrum of EBV-associated disorders of varying clonal composition that may arise in immunosuppressed organ- allograft recipients. The data are consistent with the proposal that the lymphoproliferations initiate as polyclonal expansions of EBV- carrying B cells, which progress to multiclonal lymphomas in most patients. Detection of homogeneous episomal EBV DNA in most lesions supports a primary role for the virus in the pathogenesis of these disorders.