title: Modification of cell differentiation, one of the mechanisms in the surveillance of malignancy.
abstract: Most humans carry the potentially life-endangering Epstein-Barr virus (EBV). The immediate danger after infection is imposed by proliferation of the B cells that carry the viral genome. Although a number of different cell types can be infected with EBV, B lymphocytes are exceptionally sensitive; they express a set of virus-encoded proteins, which collaborate with host proteins to induce proliferation. This phenomenon can be demonstrated in vitro with experimentally infected B cells. These viral genes are expressed only in B lymphocytes and are restricted to a defined differentiation stage. This limitation is of high importance for the maintenance of the controlled EBV-carrier state of humans. The emergence of EBV-induced B-cell malignancies is counteracted by highly efficient immunologic mechanisms. Recognition of EBV-transformed immunoblasts in an MHC class I-restricted manner by cytotoxic CD8 T cells and, to a lesser extent, by CD4 T cells, is thought to play the major role. The in vitro experimental results are in accordance with the emergence of EBV(+) B-cell malignancies in immunosuppressive conditions. In this Masters primer, we emphasize that in addition to eliminating B cells that carry the virus genome, the regulatory circuit of the immune response also operates in surveillance, particularly in the early phase of infection. This mechanism involves T-cell-mediated regulation of B-cell differentiation. Because of the strict dependence of the viral growth program on the expression of host cell factors, altering the differentiation state can curb the proliferation of B cells that harbor the viral genome.
authors: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm, Sweden. Eva.Klein@ki.se.
authors: Eva
authors: E
authors: Klein
authors: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm, Sweden.
authors: Noemi
authors: N
authors: Nagy
authors: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm, Sweden.
authors: Eahsan
authors: E
authors: Rasul
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D002051:Burkitt Lymphoma / Q000276:immunology / Q000821:virology*; D002454:Cell Differentiation / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000502:physiology; D006689:Hodgkin Disease / Q000276:immunology / Q000821:virology*; D006801:Humans; D007157:Immunologic Surveillance / Q000276:immunology*; D017735:Virus Latency / Q000276:immunology