Modification of cell differentiation, one of the mechanisms in the surveillance of malignancy

Journal Reference

Cancer Immunol Res. 2015 Feb;3(2):97-102.Klein E¹, Nagy N², Rasul E².

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¹Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm, Sweden. [email protected].

²Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm, Sweden.

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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.

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