MYC overexpression imposes a nonimmunogenic phenotype on Epstein–Barr virus-infected B cells

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The National Academy of Sciences

RESUMO

Lymphoblastoid cell lines, generated by immortalization of normal B cells by Epstein–Barr virus (EBV) in vitro, have strong antigen-presenting capacity, are sensitive to EBV-specific cytotoxic T cells, and are highly allostimulatory in mixed lymphocyte culture. By contrast, EBV-positive Burkitt lymphoma (BL) cells are poor antigen presenters, are not recognized by EBV-specific cytotoxic T cells, and are poorly allostimulatory, which raises the question of whether immunological pressure exerted during BL pathogenesis in vivo has selected for a ‘nonimmunogenic’ tumor phenotype. The present work addresses this question by examining the immunogenicity/antigenicity of cell lines, generated by conversion of a conditionally immortalized lymphoblastoid cell line to permanent growth independent of EBV-latent proteins by introduction of a constitutively active or tetracycline-regulated c-myc gene (A1 and P493–6 cells, respectively). Compared with its parental lymphoblastoid cell line, A1 cells showed many of the features of the nonimmunogenic BL phenotype, namely poor allostimulatory activity, poor antigen-presenting function associated with impaired proteasomal activity, down-regulation of peptide transporter, reduced HLA class I expression, and an inability to present endogenously expressed EBV-latent proteins to cytotoxic T cells. P493–6 cells, when grown in the presence of estrogen with the exogenous c-myc gene switched off, were strongly immunogenic. The cells had lost their immunogenic potential, however, when grown on a c-myc-driven proliferation program in the absence of estrogen. Deregulation of c-myc, a step central to the development of uncontrolled BL cell growth in vivo, can thus impose a nonimmunogenic phenotype on proliferating human B cells in the absence of any immune pressure.

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