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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4249-4252.
Prepublished online as a Blood First Edition Paper on August 25, 2005; DOI 10.1182/blood-2005-06-2327.
Previous Article | Next Article 
Submitted June 13, 2005
Accepted August 14, 2005
Epstein-Barr virus infection in vitro can rescue germinal centre B cells with inactivated immunoglobulin genes
Sridhar Chaganti, Andrew I Bell, Noelia Begue-Pastor, Anne E Milner, Mark Drayson, John Gordon, and Alan B Rickinson*
Cancer Research-UK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom
Cancer Research-UK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom; MRC Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom
* Corresponding author; email: a.b.rickinson{at}bham.ac.uk.
Immunoglobulin (Ig) genotyping of Epstein-Barr virus (EBV)-positive post-transplant lymphoproliferative disease has suggested that such lesions often arise from atypical post-germinal centre B cells, in some cases carrying functionally inactivated Ig genes. To investigate whether EBV can rescue cells that are failed products of the somatic hypermutation process occurring in germinal centres (GCs), we isolated GC cells from tonsillar cell suspensions and exposed them to EBV in vitro. Screening over 100 EBV transformed cell lines of GC origin identified six lines lacking surface Ig, a phenotype never seen among lines derived from circulating naive or memory B cells. Furthermore three of the six surface Ig-negative GC lines carried inactivating mutations in the IgH variable gene sequence. The ability of EBV to rescue aberrant products of the germinal centre reaction in vitro strengthens the probability that a parallel activity contributes to EBV's lymphomagenic potentialin vivo.

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