title: Distinct ex vivo susceptibility of B-cell subsets to epstein-barr virus infection according to differentiation status and tissue origin.
abstract: Epstein-Barr virus (EBV) uses tonsils as the portal of entry to establish persistent infection. EBV is found in various B-cell subsets in tonsils but exclusively in memory B cells in peripheral blood. The in vitro susceptibilities of B-cell subsets to EBV infection have been studied solely qualitatively. In this work, we examined quantitatively the in vitro susceptibilities of various B-cell subsets from different tissue origins to EBV infection. First, we established a centrifugation-based inoculation protocol (spinoculation) that resulted in a significantly increased proportion of infected cells compared to that obtained by conventional inoculation, enabling a detailed susceptibility analysis. Importantly, B-cell infection occurred via the known EBV receptors and infected cells showed EBV mRNA expression patterns similar to those observed after conventional inoculation, validating our approach. Tonsillar naïve and memory B cells were infected ex vivo at similar frequencies. In contrast, memory B cells from blood, which represent B cells from various lymphoid tissues, were infected at lower frequencies than their naïve counterparts. Immunoglobulin A (IgA)-positive or IgG-positive tonsillar memory B cells were significantly more susceptible to EBV infection than IgM-positive counterparts. Memory B cells were transformed with lower efficiency than naïve B cells. This result was paralleled by lower proliferation rates. In summary, these data suggest that EBV exploits the B-cell differentiation status and tissue origin to establish persistent infection.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital of Zurich, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dorner
authors.forename: Franziska
authors.initials: F
authors.lastname: Zucol
authors.forename: Christoph
authors.initials: C
authors.lastname: Berger
authors.forename: Rahel
authors.initials: R
authors.lastname: Byland
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Melroe
authors.forename: Michele
authors.initials: M
authors.lastname: Bernasconi
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Speck
authors.forename: David
authors.initials: D
authors.lastname: Nadal
mesh_terms: D016175:B-Lymphocyte Subsets / Q000821:virology*; D001769:Blood; D002454:Cell Differentiation; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000821:virology*; D006801:Humans; D007156:Immunologic Memory; D008221:Lymphoid Tissue