EBV Conference 2008 Guangzhou - Baylor College of Medicine

19 (RegID:1252; 1254; 1255)
Andrew Bell
Institution: University of Birmingham
e-mail: a.i.bell@bham.ac.uk
EPSTEIN-BARR VIRUS COLONISATION OF B CELL SUBSETS IN PRIMARY INFECTION
AND PERSISTENCE
S. Chaganti, A. Bell, C. Ma, D. Croom-Carter, E. Heath, S. Tangye, A. Hislop, W. Bergler, M. Kuo, M.
Buettner, G. Niedobitek and A.B. Rickinson
Oralabstract:
The human circulating B cell pool is composed of three populations: (i) naïve (IgD+ CD27-) cells
that have not yet engaged antigen, (ii) isotype-switched (IgD- CD27+) memory cells that arise through
antigen stimulation and germinal centre (GC) transit and (iii) non-switched (IgD+ CD27+) memory cells
whose origin remains unclear but recent evidence suggests may arise in a GC-independent manner. EBV
persists in the immune competent host by preferentially colonising class-switched memory B cells,
although how this is achieved remains unclear. In one scenario, EBV infects naïve cells and drives
their differentiation into memory via GC transit; in another, EBV avoids GCs and infects memory cells
directly. Here we report three findings which support this latter view. Firstly we analysed virus genome
loads in isolated tonsillar B cell subsets from infectious mononucleosis (IM) patients and found that EBV
loads were relatively low in CD10+ or CD77+ GC cells but were concentrated in extrafollicular B cells
expressing the GC marker CD38 as an activation antigen. Secondly we examined EBV’s colonisation of
circulating naïve, class-switched and non-switched memory B cells and found that, while
switched-memory B cells had the highest viral loads, EBV was also detectable in non-switched memory
cells both in IM patients and in some long-term virus carriers. Thirdly, we investigated EBV carriage in
patients with X-linked lymphoproliferative disease (XLP), an immunodeficiency characterised by extreme
susceptibility to EBV infection, the absence of fully-functional GC activity and the inability to generate
class-switched memory B cells. Here we found that XLP patients who survived primary infection
harboured EBV within the small population of non-switched memory B cells, rather than within the
dominant naïve population. These findings suggest that EBV can colonise the non-switched
memory B cell pool, albeit not as efficiently as it does the switched memory population, and that EBV can
establish persistence in the absence of GC transit.
EBV Conference 2008 Guangzhou
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