Epstein-Barr virus colonization of tonsillar and peripheral blood B-cell subsets in primary infection and persistence.
Epstein-Barr virus (EBV) persists in the immune host by preferentially colonizing 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 center (GC) transit; in another, EBV avoids GC transit and infects memory B cells directly. We report 2 findings consistent with this latter view. First, we examined circulating non-isotype-switched (IgD(+)CD27(+)) memory cells, a population that much evidence suggests is GC-independent in origin. Whereas isotype-switched memory had the highest viral loads by quantitative polymerase chain reaction, EBV was detectable in the nonswitched memory pool both in infectious mononucleosis (IM) patients undergoing primary infection and in most long-term virus carriers. Second, we examined colonization by EBV 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 extrafollicular B cells expressing CD38 as an activation antigen and not as a marker of ectopic GC activity.
Cancer Research UK Institute for Cancer Studies, University of Birmingham, United Kingdom.
Sridhar
S
Chaganti
Emily M
EM
Heath
Wolfgang
W
Bergler
Michael
M
Kuo
Maike
M
Buettner
Gerald
G
Niedobitek
Alan B
AB
Rickinson
Andrew I
AI
Bell
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D016175:B-Lymphocyte Subsets / Q000821:virology*; D001773:Blood Cells / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007156:Immunologic Memory; D008562:Membrane Glycoproteins / Q000032:analysis; D018448:Models, Immunological; D014066:Palatine Tonsil / Q000166:cytology / Q000821:virology*; D019562:Viral Load; D018406:Virus Physiological Phenomena
D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1