EBV persistence involves strict selection of latently infected B cells.
EBV is found preferentially in IgD- B cells in the peripheral blood. This has led to the proposal that the recirculating memory B cell pool is the site of long-lived persistent infection. In this paper we have used CD27, a newly identified specific marker for memory B cells, to test this hypothesis. We show that EBV is tightly restricted in its expression. Less than 1 in 1000 of the infected cells in the peripheral blood are naive (IgD+, CD27-) and <1 in 250 are IgD+ memory cells. Furthermore, EBV was undetectable in the self-renewing peripheral CD5+ or B1 cells, a subset that has not been through a germinal center. No such restriction was observed in tonsillar B cells. Therefore, the virus has access to a range of B cell subsets in the lymph nodes but is tightly restricted to a specific long-lived compartment of B cells, the IgD-, CD27+, and CD5- memory B cells, in the periphery. We suggest that access to this compartment is essential to allow the growth-promoting latent genes to be switched off to create a site of persistent infection that is neither pathogenic nor a target for immunosurveillance.
Joseph
A M
AM
Tufts University School of Medicine, Boston, MA 02138, USA.
Babcock
G J
GJ
Thorley-Lawson
D A
DA
D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018956:CD5 Antigens / Q000096:biosynthesis / Q000097:blood; D002460:Cell Line; D006566:Herpesviridae Infections / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007072:Immunoglobulin D / Q000096:biosynthesis / Q000097:blood; D007156:Immunologic Memory; D016130:Immunophenotyping; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000821:virology; D014407:Tumor Cells, Cultured; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000097:blood; D014412:Tumor Virus Infections / Q000276:immunology; D017735:Virus Latency / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D018956:CD5 Antigens; D007072:Immunoglobulin D; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7