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Blood, 1 November 2000, Vol. 96, No. 9, pp. 3133-3138
NEOPLASIA
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
Tilmann Spieker,
Julia Kurth,
Ralf Küppers,
Klaus Rajewsky,
Andreas Bräuninger, and
Martin-Leo Hansmann
From the Department of Pathology, University of
Frankfurt, Frankfurt, and the Institute for Genetics, University of
Cologne, Cologne, Germany.
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.

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