Molecular single-cell analysis of the clonal relationship of small Epstein-Barr virus–infected cells and Epstein-Barr virus–harboring Hodgkin and Reed/Sternberg cells in Hodgkin disease

• Published in: Blood 2000-11, Vol.96 (9), p.3133-3138
• Main Authors: Spieker, Tilmann, Kurth, Julia, Küppers, Ralf, Rajewsky, Klaus, Bräuninger, Andreas, Hansmann, Martin-Leo
• Format: Article
• Language: English
• Subjects: Adult; Aged; B-Lymphocytes - pathology; B-Lymphocytes - virology; Biological and medical sciences; Clone Cells; Gene Rearrangement; Genes, Immunoglobulin; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - physiology; Hodgkin Disease - genetics; Hodgkin Disease - immunology; Hodgkin Disease - pathology; Hodgkin Disease - virology; Humans; Immunoglobulin Variable Region - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Reed-Sternberg Cells - immunology; Reed-Sternberg Cells - pathology; Reed-Sternberg Cells - virology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V96.9.3133

Epstein-Barr virus (EBV) can be detected in the tumor cells of approximately 40% of cases of classical Hodgkin disease (cHD). Clonality studies suggest that infection of the neoplastic Hodgkin and Reed/Sternberg (HRS) cells occurs before tumor clone expansion. In EBV-positive cases, variable numbers of EBER-positive small B cells are sometimes also observed that immunohistologically differ from the neoplastic cells by lack of CD30 and latent membrane protein 1 expression. To analyze the clonal relationship between these EBV+ cells and the HRS cells, single EBV-infected CD30− B cells, as well as HRS cells from 3 cases of EBV-positive cHD were micromanipulated, their immunoglobulin gene rearrangements amplified and then compared with each other. In 2 cases, all small EBV-infected cells were clonally unrelated to the HRS cells. In a third case, 2 of 29 small CD30− cells were found to carry HRS cell-specific rearrangements. Thus, small CD30−EBV-infected B cells in cHD belong to the HRS tumor clone rarely, if at all. In all cases, small clones unrelated to the HRS cell clones were identified among the small EBV+ CD30− cells. The vast majority of small EBV+ CD30− B cells was found to carry somatically mutated V region genes, indicating that in lymph nodes of patients with HD, like in the peripheral blood of healthy individuals, EBV persists in memory B cells.