{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:29:05Z","timestamp":1791167345380,"version":"4.1.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,4,2]]},"abstract":"<jats:p>\n                    Lymphoblastoid cell lines, generated by immortalization of normal B cells by Epstein\u2013Barr virus (EBV)\n                    <jats:italic>in vitro<\/jats:italic>\n                    , 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\n                    <jats:italic>in vivo<\/jats:italic>\n                    has selected for a \u2018nonimmunogenic\u2019 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-\n                    <jats:italic>myc<\/jats:italic>\n                    gene (A1 and P493\u20136 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\u20136 cells, when grown in the presence of estrogen with the exogenous c-\n                    <jats:italic>myc<\/jats:italic>\n                    gene switched off, were strongly immunogenic. The cells had lost their immunogenic potential, however, when grown on a c-\n                    <jats:italic>myc<\/jats:italic>\n                    -driven proliferation program in the absence of estrogen. Deregulation of c-\n                    <jats:italic>myc<\/jats:italic>\n                    , a step central to the development of uncontrolled BL cell growth\n                    <jats:italic>in vivo<\/jats:italic>\n                    , can thus impose a nonimmunogenic phenotype on proliferating human B cells in the absence of any immune pressure.\n                  <\/jats:p>","DOI":"10.1073\/pnas.072495599","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"4550-4555","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":62,"title":["MYC overexpression imposes a nonimmunogenic phenotype on Epstein\u2013Barr virus-infected B cells"],"prefix":"10.1073","volume":"99","author":[{"given":"Martin S.","family":"Staege","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, Marchioninistrasse 25, D-81377 M\u00fcnchen, Germany; CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden; Labor f\u00fcr Immungenetik, Kinderpoliklinik der LMU, Paul-Heyse-Strasse 33, D-80336 M\u00fcnchen, Germany; and Forschungszentrum f\u00fcr Krebskranke..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Lee","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, Marchioninistrasse 25, D-81377 M\u00fcnchen, Germany; CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden; Labor f\u00fcr Immungenetik, Kinderpoliklinik der LMU, Paul-Heyse-Strasse 33, D-80336 M\u00fcnchen, Germany; and Forschungszentrum f\u00fcr Krebskranke..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Frisan","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, Marchioninistrasse 25, D-81377 M\u00fcnchen, Germany; CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden; Labor f\u00fcr Immungenetik, Kinderpoliklinik der LMU, Paul-Heyse-Strasse 33, D-80336 M\u00fcnchen, Germany; and Forschungszentrum f\u00fcr Krebskranke..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Mautner","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, Marchioninistrasse 25, D-81377 M\u00fcnchen, Germany; CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden; Labor f\u00fcr Immungenetik, Kinderpoliklinik der LMU, Paul-Heyse-Strasse 33, D-80336 M\u00fcnchen, Germany; and Forschungszentrum f\u00fcr Krebskranke..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Scholz","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, Marchioninistrasse 25, D-81377 M\u00fcnchen, Germany; CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden; Labor f\u00fcr Immungenetik, Kinderpoliklinik der LMU, Paul-Heyse-Strasse 33, D-80336 M\u00fcnchen, Germany; and Forschungszentrum f\u00fcr Krebskranke..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Pajic","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, Marchioninistrasse 25, D-81377 M\u00fcnchen, Germany; CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden; Labor f\u00fcr Immungenetik, Kinderpoliklinik der LMU, Paul-Heyse-Strasse 33, D-80336 M\u00fcnchen, Germany; and Forschungszentrum f\u00fcr Krebskranke..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan B.","family":"Rickinson","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, Marchioninistrasse 25, D-81377 M\u00fcnchen, Germany; CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden; Labor f\u00fcr Immungenetik, Kinderpoliklinik der LMU, Paul-Heyse-Strasse 33, D-80336 M\u00fcnchen, Germany; and Forschungszentrum f\u00fcr Krebskranke..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria G.","family":"Masucci","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, Marchioninistrasse 25, D-81377 M\u00fcnchen, Germany; CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden; Labor f\u00fcr Immungenetik, Kinderpoliklinik der LMU, Paul-Heyse-Strasse 33, D-80336 M\u00fcnchen, Germany; and Forschungszentrum f\u00fcr Krebskranke..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Polack","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum f\u00fcr Umwelt und Gesundheit, Marchioninistrasse 25, D-81377 M\u00fcnchen, Germany; CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden; Labor f\u00fcr Immungenetik, Kinderpoliklinik der LMU, Paul-Heyse-Strasse 33, D-80336 M\u00fcnchen, Germany; and Forschungszentrum f\u00fcr Krebskranke..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg 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