Identification of a sub-population of B cells that proliferates after infection with epstein-barr virus

Infection with high titers of EBV of mixed, primary B cells in different stages of differentiation occurs during primary EBV infection and in the setting of T cell-immunocompromise that predisposes to development of EBV-lymphoproliferative diseases. Using an ex vivo system that recapitulates these conditions of infection, we correlated expression of selected B cell-surface markers and intracellular cytokines with expression of EBV latency genes and cell proliferation.We identified CD23, CD58, and IL6, as molecules expressed at early times after EBV-infection. EBV differentially infected B cells into two distinct sub-populations of latently infected CD23+ cells: one fraction, marked as CD23hiCD58+IL6- by day 3, subsequently proliferated; another fraction, marked as CD23loCD58+, expressed IL6, a B cell growth factor, but failed to proliferate. High levels of LMP1, a critical viral oncoprotein, were expressed in individual CD23hiCD58+ and CD23loCD58+ cells, demonstrating that reduced levels of LMP1 did not explain the lack of proliferation of CD23loCD58+ cells. Differentiation stage of B cells did not appear to govern this dichotomy in outcome either. Memory or na？ve B cells did not exclusively give rise to either CD23hi or IL6-expressing cells; rather memory B cells gave rise to both sub-populations of cells.B cells are differentially susceptible to EBV-mediated proliferation despite expression of viral gene products known to be critical for continuous B cell growth. Cellular events, in addition to viral gene expression, likely play a critical role in determining the outcome of EBV infection. By indentifying cells predicted to undergo EBV-mediated proliferation, our study provides new avenues of investigation into EBV pathogenesis.Infection of B cells with Epstein-Barr virus (EBV) leads to proliferation and subsequent immortalization, resulting in establishment of lymphoblastoid cell lines in vitro (LCL). LCL-like cells are observed during primary EBV infection [1], i