Submitted August 26, 2008
Accepted March 16, 2009
Epstein-Barr virus colonisation of tonsillar and peripheral blood B cell subsets in primary infection and persistence
Sridhar Chaganti, Emily M Heath, Wolfgang Bergler, Michael Kuo, Maike Buettner, Gerald Niedobitek, Alan B. Rickinson*, and Andrew I. Bell
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom
Krankenhaus St. Joseph-Stift Bremen, Bremen, Germany
Birmingham Children's Hospital, Birmingham, United Kingdom
Pathological Institute, University Hospital Erlangen, Erlangen, Germany
Institute for Pathology, Sana Klinikum Lichtenberg/Unfallkrankenhaus Berlin, Berlin, Germany
* Corresponding author; email: a.b.rickinson{at}bham.ac.uk.
Epstein-Barr virus (EBV) persists in the immune host by preferentially colonising the isotype-switched (IgD- CD27+) memory B cell pool. In one scenario, this is achieved through virus infection of naive (IgD+ CD27-) B cells and their differentiation into memory via germinal centre (GC) transit; in another, EBV avoids GC transit and infects memory B cells directly. We report two findings consistent with this latter view. Firstly we examined circulating non-isotype-switched (IgD+ CD27+) memory cells, a population which much evidence suggests is GC-independent in origin. While isotype-switched memory had the highest viral loads by Q-PCR, EBV was detectable in the non-switched memory pool both in infectious mononucleosis (IM) patients undergoing primary infection and in most long-term virus carriers. Secondly we examined EBV's colonisation of B cell subsets sorted from a unique collection of IM tonsillar cell suspensions. Here viral loads were concentrated in B cells with the CD38 marker of GC origin, but lacking other GC markers CD10 and CD77. These findings, supported by histologic evidence, suggest that EBV infection in IM tonsils involves extra-follicular B cells expressing CD38 as an activation antigen and not as a marker of ectopic GC activity.
