Table of Contents Author Guidelines Submit a Manuscript
Journal of Oncology
Volume 2010 (2010), Article ID 516047, 14 pages
http://dx.doi.org/10.1155/2010/516047
Review Article

Burkitt Lymphoma: Pathogenesis and Immune Evasion

Department of Microbiology and Immunology, Charles Darby Children's Research Institute, Hollings Cancer Center, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA

Received 21 June 2010; Accepted 2 September 2010

Academic Editor: Rob S. Pieters

Copyright © 2010 Jason M. God and Azizul Haque. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. Booth, D. P. Burkitt, D. J. Bassett, R. A. Cooke, and J. Biddulph, “Burkitt lymphoma in Papua, New Guinea,” British Journal of Cancer, vol. 21, no. 4, pp. 657–664, 1967. View at Google Scholar · View at Scopus
  2. E. Klein and G. Klein, “Burkitt lymphoma,” Seminars in Cancer Biology, vol. 19, no. 6, pp. 345–346, 2009. View at Google Scholar
  3. L. de Leval and R. P. Hasserjian, “Diffuse large B-cell lymphomas and burkitt lymphoma,” Hematology/Oncology Clinics of North America, vol. 23, no. 4, pp. 791–827, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. G. W. Bornkamm, “Epstein-Barr virus and the pathogenesis of Burkitt's lymphoma: more questions than answers,” International Journal of Cancer, vol. 124, no. 8, pp. 1745–1755, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. S. M. Mbulaiteye, R. J. Biggar, K. Bhatia, M. S. Linet, and S. S. Devesa, “Sporadic childhood Burkitt lymphoma incidence in the United States during 1992–2005,” Pediatric Blood and Cancer, vol. 53, no. 3, pp. 366–370, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. C. Bellan, L. Stefano, D. F. Giulia, E. A. Rogena, and L. Lorenzo, “Burkitt lymphoma versus diffuse large B-cell lymphoma: a practical approach,” Hematological Oncology, vol. 27, no. 4, pp. 182–185, 2009. View at Publisher · View at Google Scholar
  7. A. D. Hislop, G. S. Taylor, D. Sauce, and A. B. Rickinson, “Cellular responses to viral infection in humans: lessons from Epstein-Barr virus,” Annual Review of Immunology, vol. 25, pp. 587–617, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. C. Münz and A. Moormann, “Immune escape by Epstein-Barr virus associated malignancies,” Seminars in Cancer Biology, vol. 18, no. 6, pp. 381–387, 2008. View at Publisher · View at Google Scholar · View at Scopus
  9. H. Williams and D. H. Crawford, “Epstein-Barr virus: the impact of scientific advances on clinical practice,” Blood, vol. 107, no. 3, pp. 862–869, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. F. Pietersma, E. Piriou, and D. van Baarle, “Immune surveillance of EBV-infected B cells and the development of non-Hodgkin lymphomas in immunocompromised patients,” Leukemia and Lymphoma, vol. 49, no. 6, pp. 1028–1041, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. American Cancer Society, “Cancer Facts and Figures 2009,” 2009. View at Google Scholar
  12. B. Fields, D. Knipe, and P. Howley, Fields Virology, vol. 2, Lippincott-Raven, 1996.
  13. K. Kawa, “Diagnosis and treatment of Epstein-Barr virus-associated natural killer cell lymphoproliferative disease,” International Journal of Hematology, vol. 78, no. 1, pp. 24–31, 2003. View at Google Scholar · View at Scopus
  14. A. L. Snow and O. M. Martinez, “Epstein-Barr virus: evasive maneuvers in the development of PTLD,” American Journal of Transplantation, vol. 7, no. 2, pp. 271–277, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. A. T. Deyrup, “Epstein-Barr virus-associated epithelial and mesenchymal neoplasms,” Human Pathology, vol. 39, no. 4, pp. 473–483, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. C. W. Tsang, X. Lin, N. H. Gudgeon et al., “CD4+ T-cell responses to Epstein-Barr virus nuclear antigen EBNA1 in Chinese populations are highly focused on novel C-terminal domain-derived epitopes,” Journal of Virology, vol. 80, no. 16, pp. 8263–8266, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. T. A. Haigh, X. Lin, H. Jia et al., “EBV latent membrane proteins (LMPs) 1 and 2 as immunotherapeutic targets: LMP-specific CD4+ cytotoxic T cell recognition of EBV-transformed B cell lines,” Journal of Immunology, vol. 180, no. 3, pp. 1643–1654, 2008. View at Google Scholar · View at Scopus
  18. A. B. Rickinson and D. J. Moss, “Human cytotoxic T lymphocyte responses to Epstein-Barr virus infection,” Annual Review of Immunology, vol. 15, pp. 405–431, 1997. View at Publisher · View at Google Scholar · View at Scopus
  19. G. Brady, G. J. MacArthur, and P. J. Farrell, “Epstein-Barr virus and Burkitt lymphoma,” Postgraduate Medical Journal, vol. 84, no. 993, pp. 372–377, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. B. Vennstrom, D. Sheiness, J. Zabielski, and J. M. Bishop, “Isolation and characterization of c-myc, a cellular homolog of the oncogene (v-myc) of avian myelocytomatosis virus strain 29,” Journal of Virology, vol. 42, no. 3, pp. 773–779, 1982. View at Google Scholar · View at Scopus
  21. C. V. Dang, “c-Myc target genes involved in cell growth, apoptosis, and metabolism,” Molecular and Cellular Biology, vol. 19, no. 1, pp. 1–11, 1999. View at Google Scholar · View at Scopus
  22. C. E. Nesbit, J. M. Tersak, and E. V. Prochownik, “MYC oncogenes and human neoplastic disease,” Oncogene, vol. 18, no. 19, pp. 3004–3016, 1999. View at Publisher · View at Google Scholar · View at Scopus
  23. C. V. Dang, K. A. O'Donnell, K. I. Zeller, T. Nguyen, R. C. Osthus, and F. Li, “The c-Myc target gene network,” Seminars in Cancer Biology, vol. 16, no. 4, pp. 253–264, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. M. J. Allday, “How does Epstein-Barr virus (EBV) complement the activation of Myc in the pathogenesis of Burkitt's lymphoma?” Seminars in Cancer Biology, vol. 19, no. 6, pp. 366–376, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. B. Hoffman and D. A. Liebermann, “Apoptotic signaling by c-MYC,” Oncogene, vol. 27, no. 50, pp. 6462–6472, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. V. S. Blinder, A. Chadburn, R. R. Furman, S. Mathew, and J. P. Leonard, “Review: improving outcomes for patients with Burkitt lymphoma and HIV,” AIDS Patient Care and STDs, vol. 22, no. 3, pp. 175–187, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. D. H. Wright, “What is Burkitt's lymphoma and when is it endemic?” Blood, vol. 93, no. 2, p. 758, 1999. View at Google Scholar · View at Scopus
  28. J. T. Yustein and C. V. Dang, “Biology and treatment of Burkitt's lymphoma,” Current Opinion in Hematology, vol. 14, no. 4, pp. 375–381, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. S. M. Mbulaiteye, W. F. Anderson, K. Bhatia, P. S. Rosenberg, M. S. Linet, and S. S. Devesa, “Trimodal age-specific incidence patterns for Burkitt lymphoma in the United States, 1973–2005,” International Journal of Cancer, vol. 126, no. 7, pp. 1732–1739, 2010. View at Publisher · View at Google Scholar
  30. T. Onizuka, M. Moriyama, T. Yamochi et al., “BCL-6 gene product, a 92- to 98-kD nuclear phosphoprotein, is highly expressed in germinal center B cells and their neoplastic counterparts,” Blood, vol. 86, no. 1, pp. 28–37, 1995. View at Google Scholar · View at Scopus
  31. C. J. Chapman, C. I. Mockridge, M. Rowe, A. B. Rickinson, and F. K. Stevenson, “Analysis of V(H) genes used by neoplastic B cells in endemic Burkitt's lymphoma shows somatic hypermutation and intraclonal heterogeneity,” Blood, vol. 85, no. 8, pp. 2176–2181, 1995. View at Google Scholar · View at Scopus
  32. C. J. Chapman, J. X. Zhou, C. Gregory, A. B. Rickinson, and F. K. Stevenson, “V(H) and V(L) gene analysis in sporadic Burkitt's lymphoma shows somatic hypermutation, intraclonal heterogeneity, and a role for antigen selection,” Blood, vol. 88, no. 9, pp. 3562–3568, 1996. View at Google Scholar · View at Scopus
  33. R. Küppers and R. Dalla-Favera, “Mechanisms of chromosomal translocations in B cell lymphomas,” Oncogene, vol. 20, no. 40, pp. 5580–5594, 2001. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Küppers, “B cells under influence: transformation of B cells by Epstein-Barr virus,” Nature Reviews Immunology, vol. 3, no. 10, pp. 801–812, 2003. View at Google Scholar · View at Scopus
  35. M. S. Staege, S. P. Lee, T. Frisan et al., “MYC overexpression imposes a nonimmunogenic phenotype on Epstein-Barr virus-infected B cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 7, pp. 4550–4555, 2002. View at Publisher · View at Google Scholar · View at Scopus
  36. M. L. Andersson, N. J. Stam, G. Klein, H. L. Ploegh, and M. G. Masucci, “Aberrant expression of HLA class-I antigens in Burkitt lymphoma cells,” International Journal of Cancer, vol. 47, no. 4, pp. 544–550, 1991. View at Google Scholar · View at Scopus
  37. S. Amria, C. Cameron, R. Stuart, and A. Haque, “Defects in HLA class II antigen presentation in B-cell lymphomas,” Leukemia and Lymphoma, vol. 49, no. 2, pp. 353–355, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. N. Mutalima, E. Molyneux, H. Jaffe et al., “Associations between Burkitt lymphoma among children in Malawi and infection with HIV, EBV and malaria: results from a case-control study,” PLoS ONE, vol. 3, no. 6, article e2505, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. N. Rasti, K. I. Falk, D. Donati et al., “Circulating Epstein-Barr virus in children living in malaria-endemic areas,” Scandinavian Journal of Immunology, vol. 61, no. 5, pp. 461–465, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. R. Njie, A. I. Bell, H. Jia et al., “The effects of acute malaria on Epstein-Barr virus (EBV) load and EBV-specific T cell immunity in Gambian children,” Journal of Infectious Diseases, vol. 199, no. 1, pp. 31–38, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. E. Piriou, R. Kimmel, K. Chelimo et al., “Serological evidence for long-term Epstein-Barr virus reactivation in children living in a holoendemic malaria region of Kenya,” Journal of Medical Virology, vol. 81, no. 6, pp. 1088–1093, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. A. M. Moormann, K. Chelimo, P. O. Sumba, D. J. Tisch, R. Rochford, and J. W. Kazura, “Exposure to holoendemic malaria results in suppression of Epstein-Barr virus-specific T cell immunosurveillance in Kenyan children,” Journal of Infectious Diseases, vol. 195, no. 6, pp. 799–808, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Chene, D. Donati, J. Orem et al., “Endemic Burkitt's lymphoma as a polymicrobial disease. New insights on the interaction between Plasmodium falciparum and Epstein-Barr virus,” Seminars in Cancer Biology, vol. 19, no. 6, pp. 411–420, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. K. Sebelin-Wulf, T. D. Nguyen, S. Oertel et al., “Quantitative analysis of EBV-specific CD4/CD8 T cell numbers, absolute CD4/CD8 T cell numbers and EBV load in solid organ transplant recipients with PLTD,” Transplant Immunology, vol. 17, no. 3, pp. 203–210, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. I. T. Aldoss, D. D. Weisenburger, K. Fu et al., “Adult Burkitt lymphoma: advances in diagnosis and treatment,” Oncology, vol. 22, no. 13, pp. 1508–1517, 2008. View at Google Scholar · View at Scopus
  46. C. Patte, A. Auperin, M. Gerrard et al., “Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients,” Blood, vol. 109, no. 7, pp. 2773–2780, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. I. Magrath, M. Adde, A. Shad et al., “Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen,” Journal of Clinical Oncology, vol. 14, no. 3, pp. 925–934, 1996. View at Google Scholar · View at Scopus
  48. M. Diviné, P. Casassus, S. Koscielny et al., “Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol,” Annals of Oncology, vol. 16, no. 12, pp. 1928–1935, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Di Nicola, C. Carlo-Stella, J. Mariotti et al., “High response rate and manageable toxicity with an intensive, short-term chemotherapy programme for Burkitt's lymphoma in adults,” British Journal of Haematology, vol. 126, no. 6, pp. 815–820, 2004. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Gerrard, M. S. Cairo, C. Weston et al., “Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study,” British Journal of Haematology, vol. 141, no. 6, pp. 840–847, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. M. S. Cairo, M. Gerrard, R. Sposto et al., “Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents,” Blood, vol. 109, no. 7, pp. 2736–2743, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. D. A. Thomas, S. Faderl, S. O'Brien et al., “Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia,” Cancer, vol. 106, no. 7, pp. 1569–1580, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Oriol, J.-M. Ribera, J. Bergua et al., “High-dose chemotherapy and immunotherapy in adult Burkitt lymphoma: comparison of results in human immunodeficiency virus-infected and noninfected patients,” Cancer, vol. 113, no. 1, pp. 117–125, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Carnahan, R. Stein, Z. Qu et al., “Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab,” Molecular Immunology, vol. 44, no. 6, pp. 1331–1341, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. M. A. Comito, Q. Sun, and K. G. Lucas, “Immunotherapy for Epstein-Barr virus-associated tumors,” Leukemia and Lymphoma, vol. 45, no. 10, pp. 1981–1987, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. P. G. Spear and R. Longnecker, “Herpesvirus entry: an update,” Journal of Virology, vol. 77, no. 19, pp. 10179–10185, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. M. P. McShane and R. Longnecker, “Cell-surface expression of a mutated Epstein-Barr virus glycoprotein B allows fusion independent of other viral proteins,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 50, pp. 17474–17479, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. Q. Li, M. K. Spriggs, S. Kovats et al., “Epstein-Barr virus uses HLA class II as a cofactor for infection of B lymphocytes,” Journal of Virology, vol. 71, no. 6, pp. 4657–4662, 1997. View at Google Scholar · View at Scopus
  59. K. M. Haan, S. Kyeong Lee, and R. Longnecker, “Different functional domains in the cytoplasmic tail of glycoprotein B are involved in Epstein-Barr virus-induced membrane fusion,” Virology, vol. 290, no. 1, pp. 106–114, 2001. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Szeles, K. I. Falk, S. Imreh, and G. Klein, “Visualization of alternative Epstein-Barr virus expression programs by fluorescent in situ hybridization at the cell level,” Journal of Virology, vol. 73, no. 6, pp. 5064–5069, 1999. View at Google Scholar · View at Scopus
  61. A. Carbone, A. Gloghini, and G. Dotti, “EBV-associated lymphoproliferative disorders: classification and treatment,” Oncologist, vol. 13, no. 5, pp. 577–585, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. Y. Wu, S. Maruo, M. Yajima, T. Kanda, and K. Takada, “Epstein-Barr virus (EBV)-encoded RNA 2 (EBER2) but not EBER1 plays a critical role in EBV-induced B-cell growth transformation,” Journal of Virology, vol. 81, no. 20, pp. 11236–11245, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. H. Kohlhof, F. Hampel, R. Hoffmann et al., “Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells,” Blood, vol. 113, no. 22, pp. 5506–5515, 2009. View at Publisher · View at Google Scholar · View at Scopus
  64. B. Kempkes, D. Spitkovsky, P. Jansen-Durr et al., “B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2,” EMBO Journal, vol. 14, no. 1, pp. 88–96, 1995. View at Google Scholar · View at Scopus
  65. A. J. Sinclair, I. Palmero, G. Peters, and P. J. Farrell, “EBNA-2 and EBNA-LP cooperate to cause G0 to G1 transition during immortalization of resting human B lymphocytes by Epstein-Barr virus,” EMBO Journal, vol. 13, no. 14, pp. 3321–3328, 1994. View at Google Scholar · View at Scopus
  66. R. D. Palermo, H. M. Webb, A. Gunnell, and M. J. West, “Regulation of transcription by the Epstein-Barr virus nuclear antigen EBNA 2,” Biochemical Society Transactions, vol. 36, no. 4, pp. 625–628, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. C. Kaiser, G. Laux, D. Eick, N. Jochner, G. W. Bornkamm, and B. Kempkes, “The proto-oncogene c-myc is a direct target gene of Epstein-Barr virus nuclear antigen 2,” Journal of Virology, vol. 73, no. 5, pp. 4481–4484, 1999. View at Google Scholar · View at Scopus
  68. S. Maier, G. Staffler, A. Hartmann et al., “Cellular target genes of Epstein-Barr virus nuclear antigen 2,” Journal of Virology, vol. 80, no. 19, pp. 9761–9771, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. G. Moslalos, M. Birkenbach, R. Yalamanchili, T. VanArsdale, C. Ware, and E. Kieff, “The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family,” Cell, vol. 80, no. 3, pp. 389–399, 1995. View at Google Scholar · View at Scopus
  70. D. A. Thorley-Lawson, “Epstein-Barr virus: exploiting the immune system,” Nature Reviews Immunology, vol. 1, no. 1, pp. 75–82, 2001. View at Google Scholar · View at Scopus
  71. J. Rastelli, C. Hömig-Hölzel, J. Seagal et al., “LMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1,” Blood, vol. 111, no. 3, pp. 1448–1455, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. S. Maruo, Y. Wu, S. Ishikawa, T. Kanda, D. Iwakiri, and K. Takada, “Epstein-Barr virus nuclear protein EBNA3C is required for cell cycle progression and growth maintanance of lymphoblastoid cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 51, pp. 19500–19505, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. A. Gerbitz, J. Mautner, C. Geltinger et al., “Deregulation of the proto-oncogene c-myc through t(8;22) translocation in Burkitt's lymphoma,” Oncogene, vol. 18, no. 9, pp. 1745–1753, 1999. View at Google Scholar · View at Scopus
  74. Y. Dorsett, D. F. Robbiani, M. Jankovic, B. Reina-San-Martin, T. R. Eisenreich, and M. C. Nussenzweig, “A role for AID in chromosome translocations between c-myc and the IgH variable region,” Journal of Experimental Medicine, vol. 204, no. 9, pp. 2225–2232, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. D. F. Robbiani, A. Bothmer, E. Callen et al., “AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations,” Cell, vol. 135, no. 6, pp. 1028–1038, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. C. Bellan, S. Lazzi, M. Hummel et al., “Immunoglobulin gene analysis reveals 2 distinct cells of origin for EBV-positive and EBV-negative Burkitt lymphomas,” Blood, vol. 106, no. 3, pp. 1031–1036, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. B. Shiramizu, F. Barriga, J. Neequaye et al., “Patterns of chromosomal breakpoint locations in Burkitt's lymphoma: relevance to geography and Epstein-Barr virus association,” Blood, vol. 77, no. 7, pp. 1516–1526, 1991. View at Google Scholar · View at Scopus
  78. K. Busch, T. Keller, U. Fuchs et al., “Identification of two distinct MYC breakpoint clusters and their association with various IGH breakpoint regions in the t(8;14) translocations in sporadic Burkitt-lymphoma,” Leukemia, vol. 21, no. 8, pp. 1739–1751, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. J. D. Gordan, C. B. Thompson, and M. C. Simon, “HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation,” Cancer Cell, vol. 12, no. 2, pp. 108–113, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. I. Magrath, “The pathogenesis of Burkitt's lymphoma,” Advances in Cancer Research, vol. 55, pp. 133–270, 1990. View at Google Scholar · View at Scopus
  81. G. Kennedy, J. Komano, and B. Sugden, “Epstein-Barr virus provides a survival factor to Burkitt's lymphomas,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 24, pp. 14269–14274, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Shi, J. S. Stover, L. R. Whitby, P. K. Vogt, and D. L. Boger, “Small molecule inhibitors of Myc/Max dimerization and Myc-induced cell transformation,” Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 21, pp. 6038–6041, 2009. View at Publisher · View at Google Scholar
  83. E. Leucci, M. Cocco, A. Onnis et al., “MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation,” Journal of Pathology, vol. 216, no. 4, pp. 440–450, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. A. Sharipo, M. Imreh, A. Leonchiks, S. Imreh, and M. G. Masucci, “A minimal glycine-alanine repeat prevents the interaction of ubiquitinated IκBα with the proteasome: a new mechanism for selective inhibition of proteolysis,” Nature Medicine, vol. 4, no. 8, pp. 939–944, 1998. View at Publisher · View at Google Scholar · View at Scopus
  85. Y. Yin, B. Manoury, and R. Fåhraeus, “Self-inhibition of synthesis and antigen presentation by Epstein-Barr virus-encoded EBNA1,” Science, vol. 301, no. 5638, pp. 1371–1374, 2003. View at Publisher · View at Google Scholar · View at Scopus
  86. M. Schlee, M. Hölzel, S. Bernard et al., “c-MYC activation impairs the NF-κB and the interferon response: implications for the pathogenesis of Burkitt's lymphoma,” International Journal of Cancer, vol. 120, no. 7, pp. 1387–1395, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. M. Billaud, F. Rousset, A. Calender et al., “Low expression of lymphocyte function-associated antigen (LFA)-1 and LFA-3 adhesion molecules is a common trait in Burkitt's lymphoma associated with and not associated with Epstein-Barr virus,” Blood, vol. 75, no. 9, pp. 1827–1833, 1990. View at Google Scholar · View at Scopus
  88. T. Frisan, V. Levitsky, A. Polack, and M. G. Masucci, “Phenotype-dependent differences in proteasome subunit composition and cleavage specificity in B cell lines,” Journal of Immunology, vol. 160, no. 7, pp. 3281–3289, 1998. View at Google Scholar · View at Scopus
  89. C. D. Gregory, R. J. Murray, C. F. Edwards, and A. B. Rickinson, “Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance,” Journal of Experimental Medicine, vol. 167, no. 6, pp. 1811–1824, 1988. View at Google Scholar · View at Scopus
  90. K. Klapproth, S. Sander, D. Marinkovic, B. Baumann, and T. Wirth, “The IKK2/NF-κB pathway suppresses MYC-induced lymphomagenesis,” Blood, vol. 114, no. 12, pp. 2448–2458, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. S. P. Lee, J. M. Brooks, H. Al-Jarrah et al., “CD8 T cell recognition of endogenously expressed Epstein-Barr virus nuclear antigen 1,” Journal of Experimental Medicine, vol. 199, no. 10, pp. 1409–1420, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. J. Tellam, G. Connolly, K. J. Green et al., “Endogenous presentation of CD8+ T cell epitopes from Epstein-Barr virus-encoded nuclear antigen 1,” Journal of Experimental Medicine, vol. 199, no. 10, pp. 1421–1431, 2004. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Nikiforow, K. Bottomly, G. Miller, and C. Münz, “Cytolytic CD4+-T-cell clones reactive to EBNA1 inhibit Epstein-Barr virus-induced B-cell proliferation,” Journal of Virology, vol. 77, no. 22, pp. 12088–12104, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. K. N. Heller, J. Upshaw, B. Seyoum, H. Zebroski, and C. Münz, “Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers,” Blood, vol. 109, no. 3, pp. 1138–1146, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. C. S. Leung, T. A. Haigh, L. K. Mackay, A. B. Rickinson, and G. S. Taylor, “Nuclear location of an endogenously expressed antigen, EBNA1, restricts access to macroautophagy and the range of CD4 epitope display,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 5, pp. 2165–2170, 2010. View at Publisher · View at Google Scholar
  96. C. S. Leung and G. S. Taylor, “Nuclear shelter: the influence of subcellular location on the processing of antigens by macroautophagy,” Autophagy, vol. 6, no. 4, pp. 560–561, 2010. View at Publisher · View at Google Scholar
  97. G. Kelly, A. Bell, and A. Rickinson, “Epstein-Barr virus-associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2,” Nature Medicine, vol. 8, no. 10, pp. 1098–1104, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. S. S. Dave, K. Fu, G. W. Wright et al., “Molecular diagnosis of Burkitt's lymphoma,” New England Journal of Medicine, vol. 354, no. 23, pp. 2431–2442, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. M. Hummel, S. Bentink, H. Berger et al., “A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling,” New England Journal of Medicine, vol. 354, no. 23, pp. 2419–2430, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. K. L. Csencsits and D. K. Bishop, “Contrasting alloreactive CD4+ and CD8+ T cells: there's more to it than MHC restriction,” American Journal of Transplantation, vol. 3, no. 2, pp. 107–115, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. W. Held, A. Chalifour, and J. D. Coudert, “Regulation of natural killer cell function: a role for the NK cell's own MHC class I molecules,” Medical Microbiology and Immunology, vol. 194, no. 4, pp. 169–174, 2005. View at Publisher · View at Google Scholar · View at Scopus
  102. I. A. York and K. L. Rock, “Antigen processing and presentation by the class I major histocompatibility complex,” Annual Review of Immunology, vol. 14, pp. 369–396, 1996. View at Publisher · View at Google Scholar
  103. P. M. Day, J. W. Yewdell, A. Porgador, R. N. Germain, and J. R. Bennink, “Direct delivery of exogenous MHC class I molecule-binding oligopeptides to the endoplasmic reticulum of viable cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 15, pp. 8064–8069, 1997. View at Publisher · View at Google Scholar · View at Scopus
  104. X.-L. Huang, Z. Fan, B. A. Colleton et al., “Processing and presentation of exogenous HLA class I peptides by dendritic cells from human immunodeficiency virus type 1-infected persons,” Journal of Virology, vol. 79, no. 5, pp. 3052–3062, 2005. View at Publisher · View at Google Scholar · View at Scopus
  105. R. Khanna, S. R. Burrows, P. M. Steigerwald-Mullen, D. J. Moss, M. G. Kurilla, and L. Cooper, “Targeting Epstein-Barr virus nuclear antigen 1 (EBNA1) through the class II pathway restores immune recognition by EBNA1-specific cytotoxic T lymphocytes: evidence for HLA-DM-independent processing,” International Immunology, vol. 9, no. 10, pp. 1537–1543, 1997. View at Publisher · View at Google Scholar · View at Scopus
  106. M. G. Masucci, S. Torsteinsdottir, and J. Colombani, “Down-regulation of class I HLA antigens and of the Epstein-Barr virus-encoded latent membrane protein in Burkitt lymphoma lines,” Proceedings of the National Academy of Sciences of the United States of America, vol. 84, no. 13, pp. 4567–4571, 1987. View at Google Scholar · View at Scopus
  107. R. Gavioli, P. O. De Campos-Lima, M. G. Kurilla, E. Kieff, G. Klein, and M. G. Masucci, “Recognition of the Epstein-Barr virus-encoded nuclear antigens EBNA-4 and EBNA-6 by HLA-A11-restricted cytotoxic T lymphocytes: implications for down- regulation of HLA-A11 in Burkitt lymphoma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 13, pp. 5862–5866, 1992. View at Publisher · View at Google Scholar · View at Scopus
  108. T. Frisan, Q.-J. Zhang, J. Levitskaya, M. Coram, M. G. Kurilla, and M. G. Masucci, “Defective presentation of MHC class I-restricted cytotoxic T-cell epitopes in Burkitt's lymphoma cells,” International Journal of Cancer, vol. 68, no. 2, pp. 251–258, 1996. View at Publisher · View at Google Scholar · View at Scopus
  109. W. Jilg, R. Voltz, C. Markert-Hahn, H. Mairhofer, I. Munz, and H. Wolf, “Expression of class I major histocompatibility complex antigens in Epstein-Barr virus-carrying lymphoblastoid cell lines and Burkitt lymphoma cells,” Cancer Research, vol. 51, no. 1, pp. 27–32, 1991. View at Google Scholar · View at Scopus
  110. N. Rocha and J. Neefjes, “MHC class II molecules on the move for successful antigen presentation,” EMBO Journal, vol. 27, no. 1, pp. 1–5, 2008. View at Publisher · View at Google Scholar · View at Scopus
  111. A. Haque and J. S. Blum, “New insights in antigen processing and epitope selection: development of novel immunotherapeutic stragies for cancer, autoimmunity and infectious diseases,” Journal of Biological Regulators and Homeostatic Agents, vol. 19, no. 3-4, pp. 93–104, 2005. View at Google Scholar
  112. L. J. Stern, I. Potolicchio, and L. Santambrogio, “MHC class II compartment subtypes: structure and function,” Current Opinion in Immunology, vol. 18, no. 1, pp. 64–69, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. O. J. B. Landsverk, O. Bakke, and T. F. Gregers, “MHC II and the endocytic pathway: regulation by invariant chain,” Scandinavian Journal of Immunology, vol. 70, no. 3, pp. 184–193, 2009. View at Publisher · View at Google Scholar · View at Scopus
  114. X. Chen and P. E. Jensen, “MHC class II antigen presentation and immunological abnormalities due to deficiency of MHC class II and its associated genes,” Experimental and Molecular Pathology, vol. 85, no. 1, pp. 40–44, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. M. Matloubian, R. J. Concepcion, and R. Ahmed, “CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection,” Journal of Virology, vol. 68, no. 12, pp. 8056–8063, 1994. View at Google Scholar · View at Scopus
  116. J.-Q. Mi, O. Manches, J. Wang et al., “Development of autologous cytotoxic CD4+ T clones in a human model of B-cell non-Hodgkin follicular lymphoma,” British Journal of Haematology, vol. 135, no. 3, pp. 324–335, 2006. View at Publisher · View at Google Scholar · View at Scopus
  117. A. Rudensky and C. Beers, “Lysosomal cysteine proteases and antigen presentation,” Ernst Schering Research Foundation workshop., no. 56, pp. 81–95, 2006. View at Google Scholar · View at Scopus
  118. M. Maric, B. Arunachalam, U. T. Phan et al., “Defective antigen processing in GILT-free mice,” Science, vol. 294, no. 5545, pp. 1361–1365, 2001. View at Publisher · View at Google Scholar · View at Scopus
  119. M. A. Haque, P. Li, S. K. Jackson et al., “Absence of γ-interferon-inducible lysosomal thiol reductase in melanomas disrupts T cell recognition of select immunodominant epitopes,” Journal of Experimental Medicine, vol. 195, no. 10, pp. 1267–1277, 2002. View at Publisher · View at Google Scholar
  120. O. G. Goldstein, L. M. Hajiaghamohseni, S. Amria, K. Sundaram, S. V. Reddy, and A. Haque, “Gamma-IFN-inducible-lysosomal thiol reductase modulates acidic proteases and HLA class II antigen processing in melanoma,” Cancer Immunology, Immunotherapy, vol. 57, no. 10, pp. 1461–1470, 2008. View at Publisher · View at Google Scholar · View at Scopus
  121. K. T. Hastings, R. L. Lackman, and P. Cresswell, “Functional requirements for the lysosomal thiol reductase GILT in MHC class II-restricted antigen processing,” Journal of Immunology, vol. 177, no. 12, pp. 8569–8577, 2006. View at Google Scholar · View at Scopus
  122. L. K. Denzin, J. L. Fallas, M. Prendes, and W. Yi, “Right place, right time, right peptide: DO keeps DM focused,” Immunological Reviews, vol. 207, pp. 279–292, 2005. View at Publisher · View at Google Scholar · View at Scopus
  123. S. Sadegh-Nasseri, M. Chen, K. Narayan, and M. Bouvier, “The convergent roles of tapasin and HLA-DM in antigen presentation,” Trends in Immunology, vol. 29, no. 3, pp. 141–147, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. X. Chen and P. E. Jensen, “The expression of HLA-DO (H2-O) in B lymphocytes,” Immunologic Research, vol. 29, no. 1–3, pp. 19–28, 2004. View at Google Scholar
  125. H. Khalil, F. Deshaies, A. Bellemare-Pelletier et al., “Class II transactivator-induced expression of HLA-DOβ in Hela cells,” Tissue Antigens, vol. 60, no. 5, pp. 372–382, 2002. View at Publisher · View at Google Scholar · View at Scopus
  126. C. Roucard, C. Thomas, M.-A. Pasquier et al., “In vivo and in vitro modulation of HLA-DM and HLA-DO is induced by B lymphocyte activation,” Journal of Immunology, vol. 167, no. 12, pp. 6849–6858, 2001. View at Google Scholar · View at Scopus
  127. R. Busch, C. H. Rinderknecht, S. Roh et al., “Achieving stability through editing and chaperoning: regulation of MHC class II peptide binding and expression,” Immunological Reviews, vol. 207, pp. 242–260, 2005. View at Publisher · View at Google Scholar
  128. J. Nedjic, M. Aichinger, N. Mizushima, and L. Klein, “Macroautophagy, endogenous MHC II loading and T cell selection: the benefits of breaking the rules,” Current Opinion in Immunology, vol. 21, no. 1, pp. 92–97, 2009. View at Publisher · View at Google Scholar · View at Scopus
  129. M. K. Tewari, G. Sinnathamby, D. Rajagopal, and L. C. Eisenlohr, “A cytosolic pathway for MHC class II-restricted antigen processing that is proteasome and TAP dependent,” Nature Immunology, vol. 6, no. 3, pp. 287–294, 2005. View at Publisher · View at Google Scholar · View at Scopus
  130. V. L. Crotzer and J. S. Blum, “Autophagy and its role in MHC-mediated antigen presentation,” Journal of Immunology, vol. 182, no. 6, pp. 3335–3341, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. J. D. Lünemann and C. Münz, “Autophagy in CD4+ T-cell immunity and tolerance,” Cell Death and Differentiation, vol. 16, no. 1, pp. 79–86, 2009. View at Publisher · View at Google Scholar · View at Scopus
  132. C. Paludan, D. Schmid, M. Landthaler et al., “Endogenous MHC class II processing of a viral nuclear antigen after autophagy,” Science, vol. 307, no. 5709, pp. 593–596, 2005. View at Publisher · View at Google Scholar
  133. R. Khanna, S. R. Burrows, S. A. Thomson et al., “Class I processing-defective Burkitt's lymphoma cells are recognized efficiently by CD4+ EBV-specific CTLs,” Journal of Immunology, vol. 158, no. 8, pp. 3619–3625, 1997. View at Google Scholar · View at Scopus
  134. C. Paludan, K. Bickham, S. Nikiforow et al., “Epstein-Barr nuclear antigen 1-specific CD4+ Th1 cells kill Burkitt's lymphoma cells,” Journal of Immunology, vol. 169, no. 3, pp. 1593–1603, 2002. View at Google Scholar · View at Scopus
  135. K. S. Voo, T. Fu, H. E. Heslop, M. K. Brenner, C. M. Rooney, and R.-F. Wang, “Identification of HLA-DP3-restricted peptides from EBNA1 recognized by CD4+ T cells,” Cancer Research, vol. 62, no. 24, pp. 7195–7199, 2002. View at Google Scholar · View at Scopus
  136. T. Fu, S. V. Kui, and R.-F. Wang, “Critical role of EBNA1-specific CD4+ T colls in the control of mouse Burkitt lymphoma in vivo,” Journal of Clinical Investigation, vol. 114, no. 4, pp. 542–550, 2004. View at Publisher · View at Google Scholar
  137. A. M. Moormann, K. N. Heller, K. Chelimo et al., “Children with endemic Burkitt lymphoma are deficient in EBNAl-specific IFN-γ T cell responses,” International Journal of Cancer, vol. 124, no. 7, pp. 1721–1726, 2009. View at Publisher · View at Google Scholar · View at Scopus
  138. A. M. Moormann and J. S. Lozada, “Burkitt lymphoma in uganda: 50 years of ongoing discovery,” Pediatric Blood and Cancer, vol. 52, no. 4, pp. 433–434, 2009. View at Publisher · View at Google Scholar · View at Scopus
  139. H. M. Long, T. A. Haigh, N. H. Gudgeon et al., “CD4+ T-cell responses to epstein-barr virus (EBV) latent-cycle antigens and the recognition of EBV-transformed lymphoblastoid cell lines,” Journal of Virology, vol. 79, no. 8, pp. 4896–4907, 2005. View at Publisher · View at Google Scholar · View at Scopus
  140. H. M. Long, J. Zuo, A. M. Leese et al., “CD4+ T-cell clones recognizing human lymphoma-associated antigens: generation by in vitro stimulation with autologous Epstein-Barr virus-transformed B cells,” Blood, vol. 114, no. 4, pp. 807–815, 2009. View at Publisher · View at Google Scholar · View at Scopus