Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Epstein-Barr virus: exploiting the immune system

Nature Reviews Immunology volume 1, pages 75–82 (2001)Cite this article

Abstract

In vitro, Epstein-Barr virus (EBV) will infect any resting B cell, driving it out of the resting state to become an activated proliferating lymphoblast. Paradoxically, EBV persists in vivo in a quiescent state in resting memory B cells that circulate in the peripheral blood. How does the virus get there, and with such specificity for the memory compartment? An explanation comes from the idea that two genes encoded by the virus — LMP1 and LMP2A — allow EBV to exploit the normal pathways of B-cell differentiation so that the EBV-infected B blast can become a resting memory cell.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Signalling relationship between LMP1 and CD40.
Figure 2: Signalling relationship between LMP2A and the BCR.
Figure 3: The parallels between an antigen-driven B-cell response and EBV infection.
Figure 4: Hypothetical model of how EBV persistence.
Figure 5: The positive and negative systems that maintain EBV in a stable persistent state.

Similar content being viewed by others

References

  1. Chen, F. et al. A subpopulation of normal B cells latently infected with Epstein-Barr virus resembles Burkitt lymphoma cells in expressing EBNA-1 but not EBNA-2 or LMP1. J. Virol. 69, 3752–3758 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Tierney, R. J., Steven, N., Young, L. S. & Rickinson, A. B. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J. Virol. 68, 7374–7385 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Qu, L. & Rowe, D. T. Epstein-Barr virus latent gene expression in uncultured peripheral blood lymphocytes. J. Virol. 66, 3715–3724 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Babcock, G. J., Decker, L. L., Freeman, R. B. & Thorley-Lawson, D. A. Epstein-barr virus-infected resting memory B cells, not proliferating lymphoblasts, accumulate in the peripheral blood of immunosuppressed patients. J. Exp. Med. 190, 567–576 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Joseph, A. M., Babcock, G. J. & Thorley-Lawson, D. A. EBV persistence involves strict selection of latently infected B cells. J. Immunol. 165, 2975–2981 (2000).

    CAS  PubMed  Google Scholar 

  6. Babcock, G. J., Decker, L. L., Volk, M. & Thorley-Lawson, D. A. EBV persistence in memory B cells in vivo. Immunity 9, 395–404 (1998).

    CAS  PubMed  Google Scholar 

  7. Miyashita, E. M., Yang, B., Babcock, G. J. & Thorley-Lawson, D. A. Identification of the site of Epstein-Barr virus persistence in vivo as a resting B cell. J. Virol. 71, 4882–4891 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Henle, W. & Henle, G. in The Epstein-Barr Virus (eds Epstein, M. A. & Achong, B. G.) 61–78 (Springer–Verlag, Berlin, 1979).

    Google Scholar 

  9. Khan, G., Miyashita, E. M., Yang, B., Babcock, G. J. & Thorley-Lawson, D. A. Is EBV persistence in vivo a model for B cell homeostasis? Immunity 5, 173–179 (1996).

    CAS  PubMed  Google Scholar 

  10. Yao, Q. Y., Rickinson, A. B. & Epstein, M. A. A re-examination of the Epstein-Barr virus carrier state in healthy seropositive individuals. Int. J. Cancer 35, 35–42 (1985).

    CAS  PubMed  Google Scholar 

  11. Tan, L. C. et al. A re-evaluation of the frequency of CD8+ T cells specific for EBV in healthy virus carriers. J. Immunol. 162, 1827–1835 (1999).

    CAS  PubMed  Google Scholar 

  12. Coffey, A. J. et al. Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene. Nature Genet. 20, 129–135 (1998).

    CAS  PubMed  Google Scholar 

  13. Sayos, J. et al. The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM. Nature 395, 462–469 (1998).

    CAS  PubMed  Google Scholar 

  14. Hamilton, J. K. et al. X-linked lymphoproliferative syndrome registry report. J. Pediatr. 96, 669–673 (1980).

    CAS  PubMed  Google Scholar 

  15. Purtilo, D. T., Cassel, C. K., Yang, J. P. & Harper, R. X-linked recessive progressive combined variable immunodeficiency (Duncan's disease). Lancet 1, 935–940 (1975).

    Article  CAS  PubMed  Google Scholar 

  16. Pope, J. H., Horne, M. K. & Scott, W. Transformation of foetal human leukocytes in vitro by filtrates of a human leukaemic cell line containing herpes-like virus. Int. J. Cancer 3, 857–866 (1968).

    CAS  PubMed  Google Scholar 

  17. Aman, P., Ehlin-Henriksson, B. & Klein, G. Epstein-Barr virus susceptibility of normal human B lymphocyte populations. J. Exp. Med. 159, 208–220 (1984).

    CAS  PubMed  Google Scholar 

  18. Thorley-Lawson, D. A. & Mann, K. P. Early events in Epstein-Barr virus infection provide a model for B cell activation. J. Exp. Med. 162, 45–59 (1985).

    CAS  PubMed  Google Scholar 

  19. Rickinson, A. B. & Kieff, E. in Virology 3rd edn Vol. 2 (eds Fields, B. N., Knipe, D. M., & Howley, P. M.) 2397–2446 (Lippincott–Raven, Philadelphia, 1996).

    Google Scholar 

  20. Brooks, L., Yao, Q. Y., Rickinson, A. B. & Young, L. S. Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J. Virol. 66, 2689–2697 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Babcock, J. G., Hochberg, D. & Thorley-Lawson, A. D. The expression pattern of Epstein-Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell. Immunity 13, 497–506 (2000).

    CAS  PubMed  Google Scholar 

  22. Babcock, G. J. & Thorley-Lawson, D. A. Tonsillar memory B cells, latently infected with Epstein-Barr virus, express the restricted pattern of latent genes previously found only in Epstein-Barr virus-associated tumors. Proc. Natl Acad. Sci. USA 97, 12250–12255 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Thorley-Lawson, D. A. & Babcock, G. J. A model for persistent infection with Epstein-Barr virus: the stealth virus of human B cells. Life Sci. 65, 1433–1453 (1999).

    CAS  PubMed  Google Scholar 

  24. Fahraeus, R. et al. Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma. Int. J. Cancer 42, 329–338 (1988).

    CAS  PubMed  Google Scholar 

  25. Yates, J. L., Warren, N. & Sugden, B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature 313, 812–815 (1985).

    CAS  PubMed  Google Scholar 

  26. Caldwell, R. G., Wilson, J. B., Anderson, S. J. & Longnecker, R. Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity 9, 405–411 (1998).

    CAS  PubMed  Google Scholar 

  27. Gires, O. et al. Latent membrane protein 1 of Epstein-Barr virus mimics a constitutively active receptor molecule. EMBO J. 16, 6131–6140 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. MacLennan, I. C. Germinal centers. Annu. Rev. Immunol. 12, 117–139 (1994).

    CAS  PubMed  Google Scholar 

  29. Liu, Y. J. et al. Mechanism of antigen-driven selection in germinal centres. Nature 342, 929–931 (1989).

    CAS  PubMed  Google Scholar 

  30. Liu, Y. J. & Arpin, C. Germinal center development. Immunol. Rev. 156, 111–126 (1997).

    CAS  PubMed  Google Scholar 

  31. Mosialos, G. et al. The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell 80, 389–399 (1995).

    CAS  PubMed  Google Scholar 

  32. Inoue, J. et al. Tumor necrosis factor receptor-associated factor (TRAF) family: adapter proteins that mediate cytokine signaling. Exp. Cell Res. 254, 14–24 (2000).

    CAS  PubMed  Google Scholar 

  33. Baker, S. J. & Reddy, E. P. Transducers of life and death: TNF receptor superfamily and associated proteins. Oncogene 12, 1–9 (1996).

    CAS  PubMed  Google Scholar 

  34. Banchereau, J. et al. The CD40 antigen and its ligand. Annu. Rev. Immunol. 12, 881–922 (1994).

    CAS  PubMed  Google Scholar 

  35. Kilger, E., Kieser, A., Baumann, M. & Hammerschmidt, W. Epstein-Barr virus-mediated B-cell proliferation is dependent upon latent membrane protein 1, which simulates an activated CD40 receptor. EMBO J. 17, 1700–1709 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Zimber-Strobl, U. et al. Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B cells but both it and activated CD40 can prolong their survival. EMBO J. 15, 7070–7078 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Beaufils, P., Choquet, D., Mamoun, R. Z. & Malissen, B. The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine leukaemia virus envelope protein and Epstein-Barr virus latent membrane protein 2A can elicit early and late lymphocyte activation events. EMBO J. 12, 5105–5112 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Miller, C. L. et al. Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases. Immunity 2, 155–166 (1995).

    CAS  PubMed  Google Scholar 

  39. Kurosaki, T. Genetic analysis of B cell antigen receptor signaling. Annu. Rev. Immunol. 17, 555–592 (1999).

    CAS  PubMed  Google Scholar 

  40. Maruyama, M., Lam, K. P. & Rajewsky, K. Memory B-cell persistence is independent of persisting immunizing antigen. Nature 407, 636–642 (2000).

    CAS  PubMed  Google Scholar 

  41. Lam, K. P., Kuhn, R. & Rajewsky, K. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90, 1073–1083 (1997).

    CAS  PubMed  Google Scholar 

  42. Hoagland, R. J. The transmission of infectious mononucleosis. Am. J. Med. Sci. 229, 262–272 (1955).

    CAS  PubMed  Google Scholar 

  43. Gordadze, A. V. et al. Notch1IC partially replaces EBNA2 function in B cells immortalized by Epstein-Barr virus. J. Virol. 75, 5899–5912 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Joseph, A. M., Babcock, G. J. & Thorley-Lawson, D. A. Cells expressing the Epstein-Barr virus growth program are present in and restricted to the naive B-cell subset of healthy tonsils. J. Virol. 74, 9964–9971 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Ling, P. D., Hsieh, J. J., Ruf, I. K., Rawlins, D. R. & Hayward, S. D. EBNA-2 upregulation of Epstein-Barr virus latency promoters and the cellular CD23 promoter utilizes a common targeting intermediate, CBF1. J. Virol. 68, 5375–5383 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Ansel, K. M. et al. A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406, 309–314 (2000).

    CAS  PubMed  Google Scholar 

  47. Polack, A. et al. c-myc activation renders proliferation of Epstein-Barr virus (EBV)- transformed cells independent of EBV nuclear antigen 2 and latent membrane protein 1. Proc. Natl Acad. Sci. USA 93, 10411–10416 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Hofelmayr, H., Strobl, L. J., Marschall, G., Bornkamm, G. W. & Zimber-Strobl, U. Activated Notch1 can transiently substitute for EBNA2 in the maintenance of proliferation of LMP1-expressing immortalized B cells. J. Virol. 75, 2033–2040 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Uchida, J. et al. Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses. Science 286, 300–303 (1999).

    CAS  PubMed  Google Scholar 

  50. Araujo, I. et al. Frequent expansion of Epstein-Barr virus (EBV) infected cells in germinal centres of tonsils from an area with a high incidence of EBV-associated lymphoma. J. Pathol. 187, 326–330(1999).

    CAS  PubMed  Google Scholar 

  51. Anagnostopoulos, I., Hummel, M., Kreschel, C. & Stein, H. Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus. Blood 85, 744–750 (1995).

    CAS  PubMed  Google Scholar 

  52. Kurth, J. et al. EBV-infected B cells in infectious mononucleosis: viral strategies for spreading in the B cell compartment and establishing latency. Immunity 13, 485–495 (2000).

    CAS  PubMed  Google Scholar 

  53. Selin, L. K., Varga, S. M., Wong, I. C. & Welsh, R. M. Protective heterologous antiviral immunity and enhanced immunopathogenesis mediated by memory T cell populations. J. Exp. Med. 188, 1705–1715 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Khanna, R., Moss, D. J. & Burrows, S. R. Vaccine strategies against Epstein-Barr virus-associated diseases: lessons from studies on cytotoxic T-cell-mediated immune regulation. Immunol. Rev. 170, 49–64 (1999).

    CAS  PubMed  Google Scholar 

  55. Carbone, A., Tirelli, U., Gloghini, A., Volpe, R. & Boiocchi, M. Human immunodeficiency virus-associated systemic lymphomas may be subdivided into two main groups according to Epstein-Barr viral latent gene expression. J. Clin. Oncol. 11, 1674–1681 (1993).

    CAS  PubMed  Google Scholar 

  56. Thomas, J. A. et al. Immunohistology of Epstein-Barr virus-associated antigens in B cell disorders from immunocompromised individuals. Transplantation 49, 944–953 (1990).

    CAS  PubMed  Google Scholar 

  57. Rooney, C. M. et al. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet 345, 9–13 (1995).

    CAS  PubMed  Google Scholar 

  58. Wang, D., Liebowitz, D. & Kieff, E. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell 43, 831–840 (1985).

    CAS  PubMed  Google Scholar 

  59. Staudt, L. M. The molecular and cellular origins of Hodgkin's disease. J. Exp. Med. 191, 207–212 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Oudejans, J. J. et al. Expression of Epstein-Barr virus encoded nuclear antigen 1 in benign and malignant tissues harbouring EBV. J. Clin. Pathol. 49, 897–902 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Pallesen, G., Hamilton-Dutoit, S. J., Rowe, M. & Young, L. S. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease. Lancet 337, 320–322 (1991).

    CAS  PubMed  Google Scholar 

  62. Herbst, H. et al. Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed–Sternberg cells. Proc. Natl Acad. Sci. USA 88, 4766–4770 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Niedobitek, G. et al. Immunohistochemical detection of the Epstein-Barr virus-encoded latent membrane protein 2A in Hodgkin's disease and infectious mononucleosis. Blood 90, 1664–1672 (1997).

    CAS  PubMed  Google Scholar 

  64. Hammarskjold, M. L. & Simurda, M. C. Epstein-Barr virus latent membrane protein transactivates the human immunodeficiency virus type 1 long terminal repeat through induction of NF-κB activity. J. Virol. 66, 6496–6501 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Brandtzaeg, P., Farstad I. N. & Haraldsen, G. Regional specialization in the mucosal immune system: primed cells do not always home along the same track. Immunol. Today. 20, 267–277 (1999).

    CAS  PubMed  Google Scholar 

  66. Klein, U., Rajewsky, K. & Kuppers, R. Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J. Exp. Med. 188, 1679–1689 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Artavanis-Tsakonas, S., Matsuno, K. & Fortini, M. E. Notch signaling. Science 268, 225–232 (1995).

    CAS  PubMed  Google Scholar 

  68. Sullivan, J. L. & Woda, B. A. X-linked lymphoproliferative syndrome. Immunodefic. Rev. 1, 325–347 (1989).

    CAS  PubMed  Google Scholar 

  69. Callan, M. F. et al. Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus in vivo. J. Exp. Med. 187, 1395–1402 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Epstein, M. A., Achong, B. G. & Barr, Y. M. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet 1, 702–703 (1964).

    CAS  PubMed  Google Scholar 

  71. Leder, P. in Burkitt's Lymphoma: A Human Cancer Model (eds Lenoir, G. M., O'Conor, G. T. & Olweny, C. L. M.) 341–371 (Oxford Univ. Press, New York, 1985).

    Google Scholar 

  72. Manolov, G. & Manolova, Y. Marker band in one chromosome 14 from Burkitt lymphomas. Nature 237, 33–34 (1972).

    CAS  PubMed  Google Scholar 

  73. Gregory, C. D., Rowe, M. & Rickinson, A. B. Different Epstein-Barr virus-B cell interactions in phenotypically distinct clones of a Burkitt's lymphoma cell line. J. Gen. Virol. 71, 1481–1495 (1990).

    CAS  PubMed  Google Scholar 

  74. Muir, C. S. Cancer of the head and neck. Nasopharyngeal cancer. Epidemiology and etiology. J. Am. Med. Assoc. 220, 393–394 (1972).

    CAS  Google Scholar 

  75. Andersson-Anvret, M., Forsby, N., Klein, G. & Henle, W. Relationship between the Epstein-Barr virus and undifferentiated nasopharyngeal carcinoma: correlated nucleic acid hybridization and histopathological examination. Int. J. Cancer 20, 486–494 (1977).

    CAS  PubMed  Google Scholar 

  76. Yu, M. C., Huang, T. B. & Henderson, B. E. Diet and nasopharyngeal carcinoma: a case-control study in Guangzhou, China. Int. J. Cancer 43, 1077–1082 (1989).

    CAS  PubMed  Google Scholar 

  77. Klein, G. in The Epstein-Barr virus (eds Epstein, M. A. & Achong, B. G.) 340–350 (Springer–Verlag, Berlin, 1979).

    Google Scholar 

  78. Niedobitek, G. The Epstein-Barr virus: a group 1 carcinogen? Virchows Arch. 435, 79–86 (1999).

    CAS  PubMed  Google Scholar 

  79. Thorley-Lawson, D. A. in Samter's Immunologic Diseases 6th edn (eds Austen, K. F., Frank, M. M., Atkinson, J. P. & Cantor, H.) 970–985 (Williams and Wilkins, New York, 2001).

    Google Scholar 

  80. Kaiser, C. et al. The proto-oncogene c-myc is a direct target gene of Epstein-Barr virus nuclear antigen 2. J. Virol. 73, 4481–4484 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Parker, G. A. et al. Epstein-Barr virus nuclear antigen (EBNA)3C is an immortalizing oncoprotein with similar properties to adenovirus E1A and papillomavirus E7. Oncogene 13, 2541–2549 (1996).

    CAS  PubMed  Google Scholar 

  82. Hsing, Y., Hostager, B. S. & Bishop, G. A. Characterization of CD40 signaling determinants regulating nuclear factor-κB activation in B lymphocytes. J. Immunol. 159, 4898–4906 (1997).

    CAS  PubMed  Google Scholar 

  83. Hanissian, S. H. & Geha, R. S. JAK3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells. Immunity 6, 379–387 (1997).

    CAS  PubMed  Google Scholar 

  84. Gires, O. et al. Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and activates STAT proteins. EMBO J. 18, 3064–3073 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Kieser, A. et al. Epstein-Barr virus latent membrane protein-1 triggers AP-1 activity via the c-Jun N-terminal kinase cascade. EMBO J. 16, 6478–6485 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Ishida, T. et al. Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region. J. Biol. Chem. 271, 28745–28748 (1996).

    CAS  PubMed  Google Scholar 

  87. Brodeur, S. R., Cheng, G., Baltimore, D. & Thorley-Lawson, D. A. Localization of the major NF-κB activating site and the sole TRAF3 binding site of LMP-1 defines two distinct signalling motifs. J. Biol. Chem. 272, 19777–19784 (1997).

    CAS  PubMed  Google Scholar 

  88. Izumi, K. M. & Kieff, E. D. The Epstein-Barr virus oncogene product latent membrane protein 1 engages the tumor necrosis factor receptor-associated death domain protein to mediate B lymphocyte growth transformation and activate NF- kappaB. Proc. Natl Acad. Sci. USA 94, 12592–12597 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Kieser, A., Kaiser, C. & Hammerschmidt, W. LMP1 signal transduction differs substantially from TNF receptor 1 signaling in the molecular functions of TRADD and TRAF2. EMBO J. 18, 2511–2521 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Swart, R., Ruf, I. K., Sample, J. & Longnecker, R. Latent membrane protein 2A-mediated effects on the phosphatidylinositol 3-Kinase/Akt pathway. J. Virol. 74, 10838–10845 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank R. Longknecker and S. Brodeur for discussions and suggestions in preparing the figures indicating the similarities in signalling between LMP1 and LMP2A with CD40 and the BCR. We also thank B. Schaffhausen for critical reading of the manuscript.

Author information

Authors and Affiliations

  1. the Department of Pathology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, 02111, Massachusetts, USA

    David A. Thorley-Lawson

Authors
  1. David A. Thorley-Lawson
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASES

Locuslink

CD27

CD40

CD154

JAK3

Lyn

SH2D1A

TRADD

OMIM

XLP

FURTHER INFORMATION

BioCarta

BCR signalling pathway

Frontiers in Bioscience

Immune regulation by CD40–CD40L interactions

Glossary

FOLLICULAR DENDRITIC CELL

Specialized non-haematopoietic stromal cells that reside in the follicles and germinal centres. These cells possess long dendrites, but are not related to dendritic cells, and carry intact antigen on their surface.

FOLLICULAR MANTLE

A structure formed when the naive B cells that occupy the follicle are pushed aside by an expanding germinal centre. The displaced naive B cells therefore form a 'mantle' around the germinal centre.

GERMINAL CENTRES

The structure that is formed by the expansion of antigen-activated B-cell blasts that have migrated into the follicles of lymph nodes. The B cells in these structures proliferate and the immunoglobulin genes undergo somatic hypermutation, before the cells leave as plasma cells or memory cells.

IMMUNORECEPTOR TYROSINE-BASED ACTIVATION MOTIF

(ITAM). A structural motif containing tyrosine residues, found in the cytoplasmic tails of several signalling molecules. The motif has the form Tyr-Xaa-Xaa-Leu/Ile, and the tyrosine is a target for phosphorylation by Src tyrosine kinases and subsequent binding of proteins containing SH2 domains.

LIPID RAFTS

Cholesterol-rich regions that provide ordered structure to the lipid bilayer and have the ability to include or exclude specific signalling molecules and complexes.

NASOPHARYNGEAL LYMPHOID SYSTEM

This is an expanded region of lymphoid tissue that surrounds the nasopharynx and includes the tonsil and adenoids. It serves to monitor antigens arriving through the mouth and nose and is known collectively as Waldeyer's ring.

NOTCH

A signalling system comprising highly conserved transmembrane receptors that regulate cell fate choice in the development of many cell lineages, and so are vital in the regulation of embryonic differentiation and development.

SOMATIC HYPERMUTATION

The process by which antigen-activated B cells in germinal centres mutate their rearranged immunoglobulin genes. The B cells are subsequently selected for those expressing the 'best' mutations on the basis of the ability of the surface immunoglobulin to bind antigen.

TONSILLAR CRYPTS

Invaginations of the epithelium that surround the tonsils. Unlike the skin, which acts as a barrier, the tonsillar epithelium is sponge-like to provide the maximum surface area for sampling antigen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thorley-Lawson, D. Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol 1, 75–82 (2001). https://doi.org/10.1038/35095584

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35095584

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing