JVI Accepts, published online ahead of print on 4 November 2009

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J. Virol. doi:10.1128/JVI.01780-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Germinal center B cells latently infected with Epstein-Barr virus proliferate extensively but do not expand in number.

Jill E Roughan, Charles Torgbor, and David A. Thorley-Lawson^*

Dept of Pathology, Tufts University School of Medicine, Jaharis Building, Boston MA 02111 USA

^* To whom correspondence should be addressed. Email: david.thorley-lawson{at}tufts.edu.

In this study we show that in long term persistent infection EBV infected cells undergoing a germinal center (GC) reaction in the tonsils are limited to the follicles and proliferate extensively. Despite this the absolute number of infected cells per GC remains small (average 3-4 per germinal center, range 1-9) and only about 38-55% (average 45%) of all GCs carry infected cells. The data fit a model where, on average, cells in the GC divide approximately 3 times, however only one progeny cell survives to undergo a further three divisions. Thus a fraction of cells undergo multiple rounds of division without increasing in numbers, i.e. they die at the same rate they are dividing. We conclude that EBV infected cells in the GC undergo the extensive proliferation characteristic of GC cells but the absolute number is limited either by the immune response or the availability of an essential survival factor. We suggest that this behavior is a relic of the mechanism by which EBV establishes persistence during acute infection. Lastly, expression of the viral latent protein LMP1 in GC B cells, unlike in vitro, does not directly correlate with expression of bcl-2 or bcl-6. This emphasizes our claim that observations made on the functions of EBV proteins in cell lines or in transgenic mice should be treated with skepticism unless verified in vivo.