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.
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.
Spieker
T
T
Department of Pathology, University of Frankfurt, Frankfurt, and the Institute for Genetics, University of Cologne, Cologne, Germany.
Kurth
J
J
Küppers
R
R
Rajewsky
K
K
Bräuninger
A
A
Hansmann
M L
ML
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology*; D002999:Clone Cells; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000473:pathology / Q000821:virology*
D007135:Immunoglobulin Variable Region