title: Proliferation and differentiation in isogenic populations of peripheral B cells activated by Epstein-Barr virus or T cell-derived mitogens.
abstract: Human B cells isolated from peripheral blood were activated and induced to proliferate by either Epstein-Barr virus (EBV) or the T cell-derived mitogens CD40 ligand (CD40L) plus interleukin (IL)-4. Although both populations initially proliferated as B-blasts, significant differences were revealed over a longer period. EBV infection resulted in continuously proliferating lymphoblastoid cell lines (LCLs), whereas most of the CD40L/IL-4-stimulated B cells had a finite proliferative lifespan of 3-4 weeks. Cell cycle analysis, trypan blue staining and Western blot analysis for cleavage of poly(ADP-ribose) polymerase (PARP) all demonstrated that the decrease in proliferation in CD40L/IL-4-stimulated B cells is not due to cell death. Instead, these cells arrest, accumulate in G(0)/G(1) and undergo alterations in cell surface marker expression, cellular morphology and immunoglobulin production, all consistent with plasmacytoid differentiation. In contrast, B cells infected with EBV continued to proliferate and retained a blast-like phenotype. Differences in both cytokine production and the expression of cell cycle regulators were identified between the two B-cell populations, which might contribute to the differentiation of the CD40L/IL-4-stimulated B cells and suggest potential mechanisms by which EBV may overcome this. The study has also identified a window of opportunity during which a comparison of isogenic populations of EBV- and mitogen-driven B blasts can be made.
authors.affiliation: Department of Virology and Ludwig Institute for Cancer Research, Wright-Fleming Institute, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors.forename: Jenny
authors.initials: J
authors.lastname: O'Nions
authors.affiliation: Department of Virology and Ludwig Institute for Cancer Research, Wright-Fleming Institute, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Allday
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D023201:CD40 Ligand / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D016207:Cytokines; D007136:Immunoglobulins; D008934:Mitogens; D023201:CD40 Ligand; D015847:Interleukin-4