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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4345-4350.
Prepublished online as a Blood First Edition Paper on August 30, 2005; DOI 10.1182/blood-2005-06-2342.
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Submitted June 13, 2005
Accepted August 12, 2005
Transformation of BCR-deficient germinal center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and post transplant lymphoma
Doerte Bechtel*, Julia Kurth, Claus Unkel, and Ralf Kueppers
Institute for Cell Biology (Tumor Research),, University of Duisburg-Essen, Essen, Germany
Department of Otorhinolaryngology, University of Duisburg-Essen, Essen, Germany
* Corresponding author; email: doerte.bechtel{at}uni-duisburg-essen.de.
In classical Hodgkin lymphoma (HL) and post transplant lymphoproliferative disease (PTLD), two malignancies frequently associated with Epstein-Barr virus (EBV), the tumor cells often appear to derive from B cell receptor (BCR)-deficient and therefore pre-apoptotic germinal center (GC) B cells. To test whether EBV can rescue BCR-less GC B cells, we infected human tonsillar CD77+ GC B cells in vitro with EBV. More than 60 monoclonal lymphoblastoid cell lines (LCLs) were established. Among these, 28 cell lines did not express surface immunoglobulin (sIg). Two of the sIg-negative cell lines carry obviously destructive mutations that have been introduced into originally functional VH gene rearrangements during the process of somatic hypermutation. Quantitative RT-PCR showed that in most other lines the sIg-deficiency was not simply the result of transcriptional downregulation, but was rather due to posttranscriptional defects. These findings strongly support the idea that EBV plays a central role in the pathogenesis of classical HL and PTLD by rescuing BCR-deficient, pre-apoptotic GC B cells from apoptosis, and that EBV infection renders the cells independent from survival signals normally supplied by a BCR. The monoclonal LCLs represent valuable models for early stages of lymphoma development in classical HL and PTLD.

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