A Gammaherpesvirus Bcl-2 Ortholog Blocks B Cell Receptor-Mediated Apoptosis and Promotes the Survival of Developing B Cells In Vivo

PLoS Pathogens

Volumn 10, Issue 2, 2014, Pages

  Coleman, Carrie B ^a   McGraw, Jennifer E ^a   Feldman, Emily R ^a   Roth, Alexa N ^a   Keyes, Lisa R ^a   Grau, Katrina R ^a   Cochran, Stephanie L ^a   Waldschmidt, Thomas J ^b   Liang, Chengyu ^c   Forrest, J Craig ^d   Tibbetts, Scott A ^a  

^a UNIVERSITY OF FLORIDA   (United States)

^b UNIVERSITY OF IOWA   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^d UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APOPTOSOME; B LYMPHOCYTE RECEPTOR; LIPOCORTIN 5; PROTEIN BCL 2;

ANIMAL CELL; ANIMAL CELL CULTURE; APOPTOSIS; ARTICLE; B LYMPHOCYTE; CELL DIFFERENTIATION; CELL MATURATION; CELL SURVIVAL; CONTROLLED STUDY; EPSTEIN BARR VIRUS; FLOW CYTOMETRY; FLUORESCENCE ACTIVATED CELL SORTING; GAMMAHERPESVIRINAE; HUMAN HERPESVIRUS 8; IMMUNOFLUORESCENCE MICROSCOPY; IMMUNOLOGICAL TOLERANCE; MOUSE; NONHUMAN; ORTHOLOGY; PRE B LYMPHOCYTE; VIRUS GENOME; VIRUS LATENCY; WESTERN BLOTTING;

ANIMALS; APOPTOSIS; B-LYMPHOCYTES; BLOTTING, WESTERN; CELL DIFFERENTIATION; CELL SURVIVAL; FLOW CYTOMETRY; GAMMAHERPESVIRINAE; HERPESVIRIDAE INFECTIONS; MICE; MICE, INBRED C57BL; MICROSCOPY, FLUORESCENCE; POLYMERASE CHAIN REACTION; PROTO-ONCOGENE PROTEINS C-BCL-2; RECEPTORS, ANTIGEN, B-CELL; TUMOR VIRUS INFECTIONS; VIRUS LATENCY;

EID: 84895749435     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003916     Document Type: Article

References (115)

1. Sunil-Chandra NP, Arno J, Fazakerley J, Nash AA, (1994) Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68. Am J Pathol 145: 818-826.
2. Tarakanova VL, Suarez F, Tibbetts SA, Jacoby MA, Weck KE, et al. (2005) Murine Gammaherpesvirus 68 Infection Is Associated with Lymphoproliferative Disease and Lymphoma in BALB {beta}2 Microglobulin-Deficient Mice. J Virol 79: 14668-14679 doi:10.1128/JVI.79.23.14668-14679.2005.
3. Cesarman E, (2011) Gammaherpesvirus and lymphoproliferative disorders in immunocompromised patients. Spec Issue Infect Hum Cancer 305: 163-174 doi:10.1016/j.canlet.2011.03.003.
4. Thorley-Lawson DA, Gross A, (2004) Persistence of the Epstein-Barr Virus and the Origins of Associated Lymphomas. N Engl J Med 350: 1328-1337 doi:10.1056/NEJMra032015.
5. Khan G, Miyashita EM, Yang B, Babcock GJ, Thorley-Lawson DA, (1996) Is EBV persistence in vivo a model for B cell homeostasis? Immunity 5: 173-179.
6. Flano E, Kim I-J, Woodland DL, Blackman MA, (2002) {gamma}-Herpesvirus Latency Is Preferentially Maintained in Splenic Germinal Center and Memory B Cells. J Exp Med 196: 1363-1372 doi:10.1084/jem.20020890.
7. Willer DO, Speck SH, (2003) Long-Term Latent Murine Gammaherpesvirus 68 Infection Is Preferentially Found within the Surface Immunoglobulin D-Negative Subset of Splenic B Cells In Vivo. J Virol 77: 8310-8321 doi:10.1128/JVI.77.15.8310-8321.2003.
8. Nealy MS, Coleman CB, Li H, Tibbetts SA, (2010) Use of a Virus-Encoded Enzymatic Marker Reveals that a Stable Fraction of Memory B Cells Expresses Latency-Associated Nuclear Antigen throughout Chronic Gammaherpesvirus Infection. J Virol 84: 7523-7534 doi:10.1128/JVI.02572-09.
9. Thorley-Lawson DA, (2001) Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol 1: 75-82 doi:10.1038/35095584.
10. Thorley-Lawson DA, Babcock GJ, (1999) A model for persistent infection with Epstein-Barr virus: The stealth virus of human B cells. Life Sci 65: 1433-1453 doi:10.1016/S0024-3205(99)00214-3.
11. Collins CM, Boss JM, Speck SH, (2009) Identification of Infected B-Cell Populations by Using a Recombinant Murine Gammaherpesvirus 68 Expressing a Fluorescent Protein. J Virol 83: 6484-6493 doi:10.1128/JVI.00297-09.
12. Marques S, Efstathiou S, Smith KG, Haury M, Simas JP, (2003) Selective Gene Expression of Latent Murine Gammaherpesvirus 68 in B Lymphocytes. J Virol 77: 7308-7318 doi:10.1128/JVI.77.13.7308-7318.2003.
13. Coleman CB, Nealy MS, Tibbetts SA, (2010) Immature and transitional B cells are latency reservoirs for a gammaherpesvirus. J Virol 84: 13045-13052 doi:10.1128/JVI.01455-10.
14. Allman DM, Ferguson SE, Lentz VM, Cancro MP, (1993) Peripheral B cell maturation. II. Heat-stable antigen(hi) splenic B cells are an immature developmental intermediate in the production of long-lived marrow-derived B cells. J Immunol Baltim Md 1950 151: 4431-4444.
15. Allman D, Lindsley RC, DeMuth W, Rudd K, Shinton SA, et al. (2001) Resolution of Three Nonproliferative Immature Splenic B Cell Subsets Reveals Multiple Selection Points During Peripheral B Cell Maturation. J Immunol 167: 6834-6840.
16. Rolink AG, ten Boekel E, Yamagami T, Ceredig R, Andersson J, et al. (1999) B cell development in the mouse from early progenitors to mature B cells. Immunol Lett 68: 89-93 doi:10.1016/S0165-2478(99)00035-8.
17. Hardy RR, Hayakawa K, (2001) B CELL DEVELOPMENT PATHWAYS. Annu Rev Immunol 19: 595-621 doi:10.1146/annurev.immunol.19.1.595.
18. Chung JB, Silverman M, Monroe JG, (2003) Transitional B cells: step by step towards immune competence. Trends Immunol 24: 342-348 doi:10.1016/S1471-4906(03)00119-4.
19. Pelanda R, Torres RM, (2006) Receptor editing for better or for worse. Lymph Dev Tumour Immunol 18: 184-190 doi:10.1016/j.coi.2006.01.005.
20. Gauld SB, Merrell KT, Cambier JC, (2006) Silencing of autoreactive B cells by anergy: a fresh perspective. Lymph Act Lymph Eff Funct 18: 292-297 doi:10.1016/j.coi.2006.03.015.
21. King L, Monroe J, (2000) Immunobiology of the immature B cell: plasticity in the B-cell antigen receptor-induced response fine tunes negative selection. Immunol Rev 176: 86-104 doi:10.1034/j.1600-065X.2000.00609.x.
22. Hippen KL, Schram BR, Tze LE, Pape KA, Jenkins MK, et al. (2005) In Vivo Assessment of the Relative Contributions of Deletion, Anergy, and Editing to B Cell Self-Tolerance. J Immunol 175: 909-916.
23. Sandel PC, Monroe JG, (1999) Negative Selection of Immature B Cells by Receptor Editing or Deletion Is Determined by Site of Antigen Encounter. Immunity 10: 289-299 doi:10.1016/S1074-7613(00)80029-1.
24. Wang H, Feng J, Qi C-F, Li Z, Morse HC, et al. (2007) Transitional B Cells Lose Their Ability to Receptor Edit but Retain Their Potential for Positive and Negative Selection. J Immunol 179: 7544-7552.
25. Hartley SB, Cooke MP, Fulcher DA, Harris AW, Cory S, et al. (1993) Elimination of self-reactive B lymphocytes proceeds in two stages: Arrested development and cell death. Cell 72: 325-335 doi:10.1016/0092-8674(93)90111-3.
26. Niiro H, Clark EA, (2002) Regulation of B-cell fate by antigen-receptor signals. Nat Rev Immunol 2: 945-956 doi:10.1038/nri955.
27. Carsetti R, Köhler G, Lamers MC, (1995) Transitional B cells are the target of negative selection in the B cell compartment. J Exp Med 181: 2129-2140 doi:10.1084/jem.181.6.2129.
28. Merino R, Ding L, Veis DJ, Korsmeyer SJ, Nuñez G, (1994) Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes. Embo J 13: 683-691.
29. Su TT, Guo B, Kawakami Y, Sommer K, Chae K, et al. (2002) PKC-β controls IκB kinase lipid raft recruitment and activation in response to BCR signaling. Nat Immunol 3: 780-786 doi:10.1038/ni823.
30. Su TT, Rawlings DJ, (2002) Transitional B Lymphocyte Subsets Operate as Distinct Checkpoints in Murine Splenic B Cell Development. J Immunol 168: 2101-2110.
31. Tomayko MM, Cancro MP, (1998) Long-Lived B Cells Are Distinguished by Elevated Expression of A1. J Immunol 160: 107-111.
32. Strasser A, Whittingham S, Vaux DL, Bath ML, Adams JM, et al. (1991) Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci 88: 8661-8665.
33. Lang J, Arnold B, Hammerling G, Harris AW, Korsmeyer S, et al. (1997) Enforced Bcl-2 Expression Inhibits Antigen-mediated Clonal Elimination of Peripheral B Cells in an Antigen Dose-dependent Manner and Promotes Receptor Editing in Autoreactive, Immature B Cells. J Exp Med 186: 1513-1522 doi:10.1084/jem.186.9.1513.
34. Fang W, Weintraub BC, Dunlap B, Garside P, Pape KA, et al. (1998) Self-Reactive B Lymphocytes Overexpressing Bcl-xL Escape Negative Selection and Are Tolerized by Clonal Anergy and Receptor Editing. Immunity 9: 35-45 doi:10.1016/S1074-7613(00)80586-5.
35. Henderson S, Huen D, Rowe M, Dawson C, Johnson G, et al. (1993) Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc Natl Acad Sci 90: 8479-8483.
36. Cheng EH-Y, Nicholas J, Bellows DS, Hayward GS, Guo H-G, et al. (1997) A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc Natl Acad Sci 94: 690-694.
37. Marshall WL, Yim C, Gustafson E, Graf T, Sage DR, et al. (1999) Epstein-Barr Virus Encodes a Novel Homolog of the bcl-2 Oncogene That Inhibits Apoptosis and Associates with Bax and Bak. J Virol 73: 5181-5185.
38. Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, et al. (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386: 517-521 doi:10.1038/386517a0.
39. Fanidi A, Hancock DC, Littlewood TD, (1998) Suppression of c-Myc-Induced Apoptosis by the Epstein-Barr Virus Gene Product BHRF1. J Virol 72: 8392-8395.
40. Virgin HW, Latreille P, Wamsley P, Hallsworth K, Weck KE, et al. (1997) Complete sequence and genomic analysis of murine gammaherpesvirus 68. J Virol 71: 5894-5904.
41. Wang G-H, Garvey TL, Cohen JI, (1999) The murine gammaherpesvirus-68 M11 protein inhibits Fas- and TNF- induced apoptosis. J Gen Virol 80: 2737-2740.
42. Virgin HW, Presti RM, Li X-Y, Liu C, Speck SH, (1999) Three Distinct Regions of the Murine Gammaherpesvirus 68 Genome Are Transcriptionally Active in Latently Infected Mice. J Virol 73: 2321-2332.
43. Loh J, Huang Q, Petros AM, Nettesheim D, van Dyk LF, et al. (2005) A Surface Groove Essential for Viral Bcl-2 Function During Chronic Infection In Vivo. Plos Pathog 1: e10 doi:10.1371/journal.ppat.0010010.
44. Roy DJ, Ebrahimi BC, Dutia BM, Nash AA, Stewart JP, (2000) Murine gammaherpesvirus M11 gene product inhibits apoptosis and is expressed during virus persistence. Arch Virol 145: 2411-2420 doi:10.1007/s007050070030.
45. Bellows DS, Chau BN, Lee P, Lazebnik Y, Burns WH, et al. (2000) Antiapoptotic Herpesvirus Bcl-2 Homologs Escape Caspase-Mediated Conversion to Proapoptotic Proteins. J Virol 74: 5024-5031 doi:10.1128/JVI.74.11.5024-5031.2000.
46. Sinha SC, Colbert CL, Becker N, Wei Y, Levine B, (2008) Molecular basis of the regulation of Beclin 1-dependent autophagy by the γ-herpesvirus 68 Bcl-2 homolog M11. Autophagy 4: 989-997.
47. Ku B, Woo J-S, Liang C, Lee K-H, Hong H-S, et al. (2008) Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine γ-Herpesvirus 68. Plos Pathog 4: e25 doi:10.1371/journal.ppat.0040025.
48. De Lima BD, May JS, Marques S, Simas JP, Stevenson PG, (2005) Murine gammaherpesvirus 68 bcl-2 homologue contributes to latency establishment in vivo. J Gen Virol 86: 31-40 doi:10.1099/vir.0.80480-0.
49. Hwang S, Oh S, Lee J-S, Jeong JH, et al. (2009) Viral Bcl-2-Mediated Evasion of Autophagy Aids Chronic Infection of γHerpesvirus 68. Plos Pathog 5: e1000609 doi:10.1371/journal.ppat.1000609.
50. Gangappa S, van Dyk LF, Jewett TJ, Speck SH, Virgin HW, (2002) Identification of the In Vivo Role of a Viral bcl-2. J Exp Med 195: 931-940 doi:10.1084/jem.20011825.
51. Loder F, Mutschler B, Ray RJ, Paige CJ, Sideras P, et al. (1999) B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals. J Exp Med 190: 75-89.
52. Tibbetts SA, van Dyk LF, Speck SH, Virgin HW, (2002) Immune Control of the Number and Reactivation Phenotype of Cells Latently Infected with a Gammaherpesvirus. J Virol 76: 7125-7132 doi:10.1128/JVI.76.14.7125-7132.2002.
53. Weck KE, Kim SS, Virgin HW, Speck SH, (1999) B Cells Regulate Murine Gammaherpesvirus 68 Latency. J Virol 73: 4651-4661.
54. Van Dyk LF, Virgin HW, Speck SH, (2000) The Murine Gammaherpesvirus 68 v-Cyclin Is a Critical Regulator of Reactivation from Latency. J Virol 74: 7451-7461 doi:10.1128/JVI.74.16.7451-7461.2000.
55. Roy V, Chang N-H, Cai Y, Bonventi G, Wither J, (2005) Aberrant IgM Signaling Promotes Survival of Transitional T1 B Cells and Prevents Tolerance Induction in Lupus-Prone New Zealand Black Mice. J Immunol 175: 7363-7371.
56. Kozono Y, Kotzin BL, Holers VM, (1996) Resting B cells from New Zealand Black mice demonstrate a defect in apoptosis induction following surface IgM ligation. J Immunol 156: 4498-4503.
57. Larson JD, Thurman JM, Rubtsov AV, Claypool D, Marrack P, et al. (2012) Murine gammaherpesvirus 68 infection protects lupus-prone mice from the development of autoimmunity. Proc Natl Acad Sci 109: E1092-E1100 doi:10.1073/pnas.1203019109.
58. Hasbold J, Klaus GGB, (1990) Anti-immunoglobulin antibodies induce apoptosis in immature B cell lymphomas. Eur J Immunol 20: 1685-1690 doi:10.1002/eji.1830200810.
59. Benhamou LE, Cazenave P, Sarthou P, (1990) Anti-immunoglobulins induce death by apoptosis in WEHI-231 B lymphoma cells. Eur J Immunol 20: 1405-1407 doi:10.1002/eji.1830200630.
60. Cherry SR, Biniszkiewicz D, van Parijs L, Baltimore D, Jaenisch R, (2000) Retroviral expression in embryonic stem cells and hematopoietic stem cells. Mol Cell Biol 20: 7419-7426.
61. Lieu FH, Hawley TS, Fong AZ, Hawley RG, (1997) Transmissibility of murine stem cell virus-based retroviral vectors carrying both interleukin-12 cDNAs and a third gene: implications for immune gene therapy. Cancer Gene Ther 4: 167-175.
62. Suzuki S, Chuang LF, Doi RH, Chuang RY, (2003) Morphine suppresses lymphocyte apoptosis by blocking p53-mediated death signaling. Biochem Biophys Res Commun 308: 802-808 doi:10.1016/S0006-291X(03)01472-4.
63. Kasai T, Ohguchi K, Nakashima S, Ito Y, Naganawa T, et al. (1998) Increased Activity of Oleate-Dependent Type Phospholipase D During Actinomycin D-Induced Apoptosis in Jurkat T Cells. J Immunol 161: 6469-6474.
64. Choong ML, Yang H, Lee MA, Lane DP, (2009) Specific activation of the p53 pathway by low dose actinomycin D: A new route to p53 based cyclotherapy. Cell Cycle 8: 2810-2818.
65. Shim D, Kang HY, Jeon BW, Kang SS, Chang S-I, et al. (2004) Protein kinase B inhibits apoptosis induced by actinomycin D in ECV304 cells through phosphorylation of caspase 8. Arch Biochem Biophys 425: 214-220 doi:10.1016/j.abb.2004.03.028.
66. Grabstein KH, Waldschmidt TJ, Finkelman FD, Hess BW, Alpert AR, et al. (1993) Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody. J Exp Med 178: 257-264 doi:10.1084/jem.178.1.257.
67. Milne CD, Fleming HE, Zhang Y, Paige CJ, (2004) Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin-1 during B-cell development. Immunol Rev 197: 75-88 doi:10.1111/j.0105-2896.2004.0103.x.
68. Erickson LD, Tygrett LT, Bhatia SK, Grabstein KH, Waldschmidt TJ, (1996) Differential expression of CD22 (Lyb8) on murine B cells. Int Immunol 8: 1121-1129 doi:10.1093/intimm/8.7.1121.
69. Ehtisham S, Sunil-Chandra NP, Nash AA, (1993) Pathogenesis of murine gammaherpesvirus infection in mice deficient in CD4 and CD8 T cells. J Virol 67: 5247-5252.
70. Cardin RD, Brooks JW, Sarawar SR, Doherty PC, (1996) Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells. J Exp Med 184: 863-871.
71. Flaño E, Woodland DL, Blackman MA, (1999) Requirement for CD4+ T Cells in Vβ4+CD8+ T Cell Activation Associated with Latent Murine Gammaherpesvirus Infection. J Immunol 163: 3403-3408.
72. Flaño E, Woodland DL, Blackman MA, Doherty PC, (2001) Analysis of Virus-Specific CD4+ T Cells during Long-Term Gammaherpesvirus Infection. J Virol 75: 7744-7748 doi:10.1128/JVI.75.16.7744-7748.2001.
73. Freeman ML, Burkum CE, Lanzer KG, Jensen MK, Ahmed M, et al. (2011) Cutting Edge: Activation of Virus-Specific CD4 T Cells throughout γ-Herpesvirus Latency. J Immunol 187: 6180-6184 doi:10.4049/jimmunol.1102745.
74. Chen T, Hudnall SD, (2006) Anatomical mapping of human herpesvirus reservoirs of infection. Mod Pathol 19: 726-737.
75. Corbellino M, Poirel L, Bestetti G, Pizzuto M, Aubin JT, et al. (1996) Restricted Tissue Distribution of Extralesional Kaposi's Sarcoma-Associated Herpesvirus-Like DNA Sequences in AIDS Patients with Kaposi's Sarcoma. Aids Res Hum Retroviruses 12: 651-657 doi:10.1089/aid.1996.12.651.
76. Luppi M, Barozzi P, Schulz TF, Setti G, Staskus K, et al. (2000) Bone Marrow Failure Associated with Human Herpesvirus 8 Infection after Transplantation. N Engl J Med 343: 1378-1385 doi:10.1056/NEJM200011093431905.
77. Kikuta H, Sakiyama Y, Matsumoto S, Oh-Ishi T, Nakano T, et al. (1993) Fatal Epstein-Barr virus-associated hemophagocytic syndrome. Blood 82: 3259-3264.
78. Hoang MP, Dawson DB, Rogers ZR, Scheuermann RH, Rogers BB, (1998) Polymerase chain reaction amplification of archival material for epstein-barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19 in children with bone marrow hemophagocytosis. Hum Pathol 29: 1074-1077 doi:10.1016/S0046-8177(98)90416-6.
79. Frizzera G, Hanto DW, Gajl-Peczalska KJ, Rosai J, McKenna RW, et al. (1981) Polymorphic diffuse B-cell hyperplasias and lymphomas in renal transplant recipients. Cancer Res 41: 4262-4279.
80. Hanto DW, Frizzera G, Gajl-Peczalska KJ, Simmons RL, (1985) Epstein-Barr virus, immunodeficiency, and B cell lymphoproliferation. Transplantation 39: 461-472.
81. Purtilo D (1984) Immune Deficiency and Cancer: Epstein-Barr Virus and Lymphoproliferative Malignancies. Springer.
82. Shapiro RS, McClain K, Frizzera G, Gajl-Peczalska KJ, Kersey JH, et al. (1988) Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation. Blood 71: 1234-1243.
83. Watanabe H, Koide M, Fukuchi K, Takagi Y, Tomoyasu S, et al. (1997) Presence of Epstein-Barr virus genome in the bone marrow of patients with hematopoietic malignancies. Acta Haematol 98: 32-36.
84. Zutter MM, Martin PJ, Sale GE, Shulman HM, Fisher L, et al. (1988) Epstein-Barr virus lymphoproliferation after bone marrow transplantation. Blood 72: 520-529.
85. Grillot DA, Merino R, Pena JC, Fanslow WC, Finkelman FD, et al. (1996) Bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice. J Exp Med 183: 381-391 doi:10.1084/jem.183.2.381.
86. Flano E, Husain SM, Sample JT, Woodland DL, Blackman MA, (2000) Latent Murine {gamma}-Herpesvirus Infection Is Established in Activated B Cells, Dendritic Cells, and Macrophages. J Immunol 165: 1074-1081.
87. Flano E, Kim I-J, Moore J, Woodland DL, Blackman MA, (2003) Differential {gamma}-Herpesvirus Distribution in Distinct Anatomical Locations and Cell Subsets During Persistent Infection in Mice. J Immunol 170: 3828-3834.
88. Weck KE, Kim SS, Virgin HW, Speck SH, (1999) Macrophages Are the Major Reservoir of Latent Murine Gammaherpesvirus 68 in Peritoneal Cells. J Virol 73: 3273-3283.
89. Watanabe K, Ichinose S, Hayashizaki K, Tsubata T, (2008) Induction of autophagy by B cell antigen receptor stimulation and its inhibition by costimulation. Biochem Biophys Res Commun 374: 274-281 doi:10.1016/j.bbrc.2008.07.013.
90. McLeod IX, He Y, (2010) Roles of autophagy in lymphocytes: reflections and directions. Cell Mol Immunol 7: 104-107 doi:10.1038/cmi.2009.115.
91. Tangye SG, Tarlinton DM, (2009) Memory B cells: Effectors of long-lived immune responses. Eur J Immunol 39: 2065-2075 doi:10.1002/eji.200939531.
92. Maruyama M, Lam KP, Rajewsky K, (2000) Memory B-cell persistence is independent of persisting immunizing antigen. Nature 407: 636-642 doi:10.1038/35036600.
93. Crotty S, Felgner P, Davies H, Glidewell J, Villarreal L, et al. (2003) Cutting edge: long-term B cell memory in humans after smallpox vaccination. J Immunol Baltim Md 1950 171: 4969-4973.
94. Gray D, Skarvall H, (1988) B-cell memory is short-lived in the absence of antigen. Nature 336: 70-73 doi:10.1038/336070a0.
95. Doherty PC, Christensen JP, Belz GT, Stevenson PG, Sangster MY, (2001) Dissecting the host response to a gamma-herpesvirus. Philos Trans R Soc Lond B Biol Sci 356: 581-593 doi:10.1098/rstb.2000.0786.
96. Stevenson PG, May JS, Smith XG, Marques S, Adler H, et al. (2002) K3-mediated evasion of CD8(+) T cells aids amplification of a latent gamma-herpesvirus. Nat Immunol 3: 733-740 doi:10.1038/ni818.
97. Ragona G, Tabilio A, Fruscalzo A, Annino L, Angeloni A, et al. (1988) Presence of EBV infected cells in the bone marrow from transplant donors. In: Ablashi DV, Ariad A, Krueger GRF, Pagano JS, Pearson GR, editors. Epstein-Barr Virus and Human Disease. Clifton, NJ: Humana Press. pp. 231-235.
98. Deeg HJ, Socie G, (1998) Malignancies After Hematopoietic Stem Cell Transplantation: Many Questions, Some Answers. Blood 91: 1833-1844.
99. Henry M, Uthman A, Geusau A, Rieger A, Furci L, et al. (1999) Infection of Circulating CD34+ Cells by HHV-8 in Patients with Kaposi/'s Sarcoma. 113: 613-616.
100. Bertolini L, Falzetti F, Lanzilli G, Moscone O, Longo M, et al. (1991) Lymphocyte receptors as differentiation markers in a cell line autonomously arisen "in vitro" from a human normal bone marrow. In: Wegmann RJ, Wegmann MA, editors. Recent Advances in Cellular and Molecular Biology. Leuven, Belgium: Peeter Press, Vol. 1. pp. 77-89.
101. Bertolini L, Aebischer ML, Ameglio F, Angeloni A, Delaroche I, et al. (2005) Phenotypic and genotypic characteristics of new euploid-diploid lymphoblastoid B cell lines EBV+, normal human bone marrow derived, spontaneously overgrown in vitro. J Virol Methods 126: 91-100 doi:10.1016/j.jviromet.2005.01.029.
102. Pavlova BG, Mühlberger HH, Strobl H, Grill R, Haslberger A, et al. (1995) B lymphocytes with latent EBV infection appearing in long-term bone marrow cultures (HLTBMCs) from haematological patients induce lysis of stromal microenvironment. Br J Haematol 89: 704-711.
103. Facer CA, Playfair JH, (1989) Malaria, Epstein-Barr virus, and the genesis of lymphomas. Adv Cancer Res 53: 33-72.
104. Morrow RH Jr, (1985) Epidemiological evidence for the role of falciparum malaria in the pathogenesis of Burkitt's lymphoma. Iarc Sci Publ pp. 177-186.
105. Asito AS, Piriou E, Jura WG, Ouma C, Odada PS, et al. (2011) Suppression of circulating IgD+CD27+ memory B cells in infants living in a malaria-endemic region of Kenya. Malar J 10: 362 doi:10.1186/1475-2875-10-362.
106. Piriou E, Asito AS, Sumba PO, Fiore N, Middeldorp JM, et al. (2012) Early Age at Time of Primary Epstein-Barr Virus Infection Results in Poorly Controlled Viral Infection in Infants From Western Kenya: Clues to the Etiology of Endemic Burkitt Lymphoma. J Infect Dis 205: 906-913 doi:10.1093/infdis/jir872.
107. Dehee A, Asselot C, Piolot T, Jacomet C, Rozenbaum W, et al. (2001) Quantification of Epstein-Barr virus load in peripheral blood of human immunodeficiency virus-infected patients using real-time PCR. J Med Virol 65: 543-552 doi:10.1002/jmv.2071.
108. Richard Y, Amiel C, Jeantils V, Mestivier D, Portier A, et al. (2010) Changes in Blood B Cell Phenotypes and Epstein-Barr Virus Load in Chronically Human Immunodeficiency Virus-Infected Patients before and after Antiretroviral Therapy. J Infect Dis 202: 1424-1434 doi:10.1086/656479.
109. Toussirot É, Roudier J, (2008) Epstein-Barr virus in autoimmune diseases. Best Pract Res Clin Rheumatol 22: 883-896 doi:10.1016/j.berh.2008.09.007.
110. Posnett DN, (2008) Herpesviruses and autoimmunity. Curr Opin Investig Drugs Lond Engl 2000 9: 505-514.
111. Getahun A, Smith MJ, Kogut I, Dyk LFvan, Cambier JC, (2012) Retention of Anergy and Inhibition of Antibody Responses during Acute Gammaherpesvirus 68 Infection. J Immunol 189: 2965-2974 doi:10.4049/jimmunol.1201407.
112. Smith KA, Efstathiou S, Cooke A, (2007) Murine gammaherpesvirus-68 infection alters self-antigen presentation and type 1 diabetes onset in NOD mice. J Immunol Baltim Md 1950 179: 7325-7333.
113. Yarilin DA, Valiando J, Posnett DN, (2004) A Mouse Herpesvirus Induces Relapse of Experimental Autoimmune Arthritis by Infection of the Inflammatory Target Tissue. J Immunol 173: 5238-5246.
114. Peacock JW, Elsawa SF, Petty CC, Hickey WF, Bost KL, (2003) Exacerbation of experimental autoimmune encephalomyelitis in rodents infected with murine gammaherpesvirus-68. Eur J Immunol 33: 1849-1858 doi:10.1002/eji.200323148.
115. Li H, Ikuta K, Sixbey JW, Tibbetts SA, (2008) A Replication-Defective Gammaherpesvirus Efficiently Establishes Long-Term Latency in Macrophages but Not in B Cells In Vivo. J Virol 82: 8500-8508 doi:10.1128/JVI.00186-08.