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Lifespan of lymphocytes

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Abstract

T and B lymphocytes comprise heterogeneous populations of cells at various stages of differentiation and activation. T-and B-cell subsets have different roles in the maintenance of immune homeostasis, and their functional differences are reflected by their respective lifespans. This review briefly summarizes the available data on lymphocyte lifespan, including the kinetics of T- and B-cell development in the primary lymphoid organs and the proliferative behavior of naive, effector and memory lymphocytes in the peripheral lymphoid compartment.

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References

  1. von Boehmer H: Positive selection of lymphocytes. Cell 1994;76:219.

    Article  Google Scholar 

  2. Nossal GJV: Negative selection of lymphocytes. Cell 1994;76:229.

    Article  PubMed  CAS  Google Scholar 

  3. Everett NB, Caffrey RW, Rieke WO: Recirculation of lymphocytes. Ann NY Acad Sci 1964;113:887.

    Article  PubMed  CAS  Google Scholar 

  4. Matsuyama M, Wiadrowski MN, Metcalf D: Autoradiographic analysis of lymphopoiesis and lymphocyte migration in mice bearing multiple thymus grafts. J Exp Med 1966; 123:559.

    Article  PubMed  CAS  Google Scholar 

  5. Bryant BJ: Renewal and fate in the mammalian thymus: Mechanisms and inferences of thymocytokinetics. Eur J Immunol 1972;2:38.

    Article  PubMed  CAS  Google Scholar 

  6. Shortman K, Jackson H: The differentiation of T lymphocytes. I. Proliferation kinetics and interrelationships of subpopulations of mouse thymus cells. Cell Immunol 1974; 12:230.

    Article  PubMed  CAS  Google Scholar 

  7. Scollay RG, Butcher EC, Weissman IL: Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur J Immunol 1980;10:210.

    Article  PubMed  CAS  Google Scholar 

  8. Scollay R, Shortman K: Cell traffic in the adult thymus: Cell entry and exit, cell birth and death; in Watson JD, Marbrook J (eds): Recognition and Regulation in Cell Mediated Immunity. New York, Dekker, 1985, p. 3.

    Google Scholar 

  9. Egerton, M, Scollay R, Shortman K: Kinetics of mature T-cell development in the thymus. Proc Natl Acad Sci USA 1990;87:2579.

    Article  PubMed  CAS  Google Scholar 

  10. Huesmann M, Scott B, Kisielow P, von Boehmer H: Kinetics and efficacy of positive selection in the thymus of normal and T cell receptor transgenic mice. Cell 1991;66:533.

    Article  PubMed  CAS  Google Scholar 

  11. Hogquist KA, Jameson SC, Heath WR, Howard JL, Bevan MJ, Carbone FR: T cell receptor antagonist peptides induce positive selection. Cell 1994;76:17.

    Article  PubMed  CAS  Google Scholar 

  12. Ashton-Rickardt PG, Bandeira A, Delaney JR, Kaer LV, Pircher HP, Zinkernagel RM, Tonegawa S: Evidence for a differential avidity model of T cell selection in the thymus. Cell 1994;76:651.

    Article  PubMed  CAS  Google Scholar 

  13. Groettrup M, Ungewiss K, Azogui O, Palacios R, Owen MJ, Hayday AC, von Boehmer H: A novel disulfide-linked heterodimer on pre-T cells consists of the T cell receptor β chain and a 33 kD glycoprotein. Cell 1993;75:283.

    Article  PubMed  CAS  Google Scholar 

  14. Mombaerts P, Clarke AR, Rudnicki MA, Iacomini J, Itohara S, Lafaille JJ, Wang L, Ichikawa Y, Jaenisch R, Hooper ML, Tonegawa S: Mutations in T-cell antigen receptor genes α and β block thymocyte development at different stages. Nature 1992;360:225.

    Article  PubMed  CAS  Google Scholar 

  15. Osmond DG, Nossal GJV: Differentiation of lymphocytes in mouse bone marrow: II. Kinetics of maturation and renewal of antiglobulin-binding cells studied by double labeling. Cell Immunol 1974;13:132.

    Article  PubMed  CAS  Google Scholar 

  16. Lassila O: Emigration of B cells from chicken bursa of Fabricius. Eur J Immunol 1989;19:955.

    Article  PubMed  CAS  Google Scholar 

  17. Pabst R, Reynolds JD: Evidence of extensive lymphocyte death in sheep Peyer’s patches. II. The number and fate of newly-formed lymphocytes that emigrate from Peyer’s patches. J Immunol 1986;136:2011.

    PubMed  CAS  Google Scholar 

  18. Opstelten D, Osmond DG: Pre-B cells in mouse bone marrow: Immunofluorescence stathmokinetic studies of the proliferation of cytoplasmice μ-chain-bearing cells in normal mice. J Immunol 1983;131:2635.

    PubMed  CAS  Google Scholar 

  19. Deenen GJ, Van Balen I, Opstelten D: In rat B lymphocyte genesis sixty percent is lost from the bone marrow at the transition of nondividing pre-B cell to sIgM+ B lymphocyte, the stage of Ig light chain gene expression. Eur J Immunol 1990;20: 557.

    Article  PubMed  CAS  Google Scholar 

  20. Gu H, Tarlinton D, Müller W, Rajewsky K, Förster I: Most peripheral B cells in mice are ligand selected. J Exp Med 1991;173:1357.

    Article  PubMed  CAS  Google Scholar 

  21. Kitamura D, Roes J, Kühn R, Rajewsky K: A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin μ chain gene. Nature 1991;350:423.

    Article  PubMed  CAS  Google Scholar 

  22. Melchers F, Karasuyama H, Haasner D, Bauer S, Kudo A, Sakaguchi N, Jameson B, Rolink A: The surrogate light chain in B-cell development. Immunol Today 1993;14:60.

    Article  PubMed  CAS  Google Scholar 

  23. Lawton AR, Cooper MD: Modification of B lymphocyte differentiation by anti-immunoglobulins. Contemp Top Immunobiol 1974;3:193.

    PubMed  CAS  Google Scholar 

  24. Nemazee DA, Bürki K: Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature 1989;337: 562.

    Article  PubMed  CAS  Google Scholar 

  25. Hartley SB, Crosbie J, Brink R, Kantor AA, Basten A, Goodnow CC: Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens. Nature 1991; 353:765.

    Article  PubMed  CAS  Google Scholar 

  26. Fulcher DA, Basten A: Reduced life-span of anergic self-reactive B cells in a double-transgenic model. J Exp Med 1994;179:125.

    Article  PubMed  CAS  Google Scholar 

  27. Tough DF, Sprent J: Turnover of naive- and memory-phenotype T cells. J Exp Med 1994;179:1127.

    Article  PubMed  CAS  Google Scholar 

  28. Kelly KA, Scollay R: Analysis of recent thymic emigrants with subset- and maturity-related markers. Int Immunol 1990;2:419.

    Article  PubMed  CAS  Google Scholar 

  29. Hosseinzadeh H, Goldschneider I: Recent thymic emigrants in the rat express a unique antigenic phenotype and undergo post-thymic maturation in peripheral lymphoid tissues J Immunol 1993;150:1670.

    PubMed  CAS  Google Scholar 

  30. Yang C, Bell EB: Functional maturation of recent thymic emigrants in the periphery: Development of alloreactivity correlates with the cyclic expression of CD45RC isoforms. Eur J Immunol 1992;22:2261.

    Article  PubMed  CAS  Google Scholar 

  31. Miller JFAP, Mitchell GF: Thymus and antigen-reactive cells. Transplant Rev 1969;1:3.

    PubMed  CAS  Google Scholar 

  32. Sprent J, Schaefer M, Hurd M, Surh CD, Ron Y: Mature murine B and T cells transferred to scid mice can survive indefinitely and many maintain a virgin phenotype. J Exp Med 1991;174:717.

    Article  PubMed  CAS  Google Scholar 

  33. Freitas AA, Rocha BB: Lymphocyte lifespans: Homeostasis, selection and competition. Immunol Today 1993;14:25.

    Article  PubMed  CAS  Google Scholar 

  34. Rocha B, Freitas AA, Coutinho AA: Population dynamics of T lymphocytes. Renewal rate and expansion in the peripheral organs. J Immunol 1983;131:2158.

    PubMed  CAS  Google Scholar 

  35. Sprent J: Lifespans of naive, memory and effector lymphocytes. Curr Opin Immunol 1993;5:433.

    Article  PubMed  CAS  Google Scholar 

  36. Norman A, Sasaki MS, Ottoman RE, Fingerhut AG: Lymphocyte lifetime in women. Science 1965; 147:745.

    Article  PubMed  CAS  Google Scholar 

  37. Buckton KE, Court Brown WM, Smith PG: Lymphocyte survival in men treated with x-rays for ankylosing spondylitis. Nature 1967;214: 470.

    Article  PubMed  CAS  Google Scholar 

  38. Michie CA, McLean A, Alcock C, Beverley PCL: Lifespan of human lymphocyte subsets defined by CD45 isoforms. Nature 1992;360: 264.

    Article  PubMed  CAS  Google Scholar 

  39. von Boehmer H, Hafen K: The life span of naive α/β T cells in secondary lymphoid organs. J Exp Med 1993;177:891.

    Article  Google Scholar 

  40. Sprent J: T and B memory cells. Cell 1994;76:315.

    Article  PubMed  CAS  Google Scholar 

  41. Unutmaz D, Pileri P, Abrignani S: Antigen-independent activation of naive and memory resting T cells by a cytokine combination. J Exp Med 1994;180:1159.

    Article  PubMed  CAS  Google Scholar 

  42. Yang H, Dundon PL, Nahill SR, Welsh RM: Virus-induced polyclonal cytotoxic T lymphocyte stimulation. J Immunol 1989;142:1710.

    PubMed  CAS  Google Scholar 

  43. Motyka B, Reynolds JD: Apoptosis is associated with the extensive B cell death in the sheep ileal peyer’s patch and the chicken bursa of Fabricius: A possible role in B cell selection. Eur J Immunol 1991;21: 1951.

    Article  PubMed  CAS  Google Scholar 

  44. Osmond DG: The turnover of B-cell populations. Immunol Today 1993; 14:34.

    Article  PubMed  CAS  Google Scholar 

  45. Chan EYT, MacLennan ICM: Only a small proportion of splenic B cells in adults are short-lived virgin cells. Eur J Immunol 1993;23:357.

    Article  PubMed  CAS  Google Scholar 

  46. Gray D: Population kinetics of rat peripheral B cells. J Exp Med 1988; 167:805.

    Article  PubMed  CAS  Google Scholar 

  47. MacLennan I, Chan E: The dynamic relationship between B-cell populations in adults. Immunol Today 1993;14:29.

    Article  PubMed  CAS  Google Scholar 

  48. Pietrangeli CE, Osmond DG: Regulation of B-lymphocyte production in the bone marrow: Medication of the effects of exogeneous stimulants by adoptively transferred spleen cells. Cell Immunol 1987;107:348.

    Article  PubMed  CAS  Google Scholar 

  49. Freitas AA, Rocha B, Forni L, Coutinho A: Population dynamics of B lymphocytes and their precursors: Demonstration of high turnover in the central and peripheral lymphoid organs. J Immunol 1982;128:54.

    PubMed  CAS  Google Scholar 

  50. Freitas AA, Coutinho A: Very rapid decay of mature B lymphocytes in the spleen. J Exp Med 1981;154: 994.

    Article  PubMed  Google Scholar 

  51. Anderson J, Coutinho A, Melchers F: Frequencies of mitogen reactive B cells in the mouse. I. Distribution in different lymphoid organs from different inbred strains of mice. J Exp Med 1977;145:1511.

    Article  Google Scholar 

  52. Sprent J, Basten A: Circulating T and B lymphocytes of the mouse. II. Lifespan. Cell Immunol 1973;7:40.

    Article  PubMed  CAS  Google Scholar 

  53. Förster I, Rajewsky K: The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow. Proc Natl Acad Sci USA 1990;87:4781.

    Article  PubMed  Google Scholar 

  54. Allman DM, Ferguson SE, Lentz VM, Cancro MP: Peripheral B cell maturation. II. Heat-stable antigenhi splenic B cells are an immature development intermediate in the production of long-lived marrow derived B cells. J Immunol 1993;151: 4431.

    PubMed  CAS  Google Scholar 

  55. Ying-zi C, Rabin E, Wortis HH: Treatment of murine CD5 B cells with anti-Ig, but not LPS, induces surface CD5: Two B-cell activation pathways. Int Immunol 1991;3:467.

    Article  Google Scholar 

  56. Deenen GJ, Kroese FGM: Kinetics of B cell subpopulations in peripheral lymphoid tissues: evidence for the presence of phenotypically distinct short-lived and long-lived B cell subsets. Int Immunol 1993;5:735.

    Article  PubMed  CAS  Google Scholar 

  57. Webb S, Morris C, Sprent J: Extrathymic tolerance of mature T cells: Clonal elimination as a consequence of immunity. Cell 1990;63:1249.

    Article  PubMed  CAS  Google Scholar 

  58. Kawabe Y, Ochi A: Programmed cell death and extrathymic reduction of Vβ8+ CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B. Nature 1991;349: 245.

    Article  PubMed  CAS  Google Scholar 

  59. Moskophidis D, Lechner F, Pircher H, Zinkernagel RM: Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. Nature 1993;362:758.

    Article  PubMed  CAS  Google Scholar 

  60. Rocha B, von Boehmer H: Peripheral selection of the T cell repertoire. Science 1991;251:1225.

    Article  PubMed  CAS  Google Scholar 

  61. Sprent J: Fate of H-2-activated T lymphocytes in syngeneic hosts. I. Fate in lymphoid tissues and intestines traced with3H-thymidine,125I-deoxyuridine and51chromium. Cell Immunol 1976;21:278.

    Article  PubMed  CAS  Google Scholar 

  62. Liu Y-J, Zhang J, Lane PJL, Chan EY-T, Maclennan ICM: Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cell-indepencent antigens. Eur J Immunol 1991;21: 2591.

    Article  Google Scholar 

  63. Liu Y-J, Joshua DE, Williams GT, Smith CA, Gordon J, MacLennan ICM: Mechanisms of antigen-drive selection in germinal centers. Nature 1989;342:929.

    Article  PubMed  CAS  Google Scholar 

  64. Ho F, Lortan JE, MacLennan ICM, Kkan M: Distinct short-lived and long-lived antibody-producing cell populations. Eur J Immunol 1986; 16:1297.

    Article  PubMed  CAS  Google Scholar 

  65. Gray D, Skarvall H: B-cell memory is short lived in the absence of antigen. Nature 1988;336:70.

    Article  PubMed  CAS  Google Scholar 

  66. Gray D, Skarvall H: B-cell memory is short-lived in the absence of antigen. J Exp Med 1974;174:969.

    Article  Google Scholar 

  67. Lau LL, Jamieson BD, Somasundaram T, Ahmed R: Cytotoxic T-cell memory without antigen. Nature 1994;369:648.

    Article  PubMed  CAS  Google Scholar 

  68. Hou S, Hyland L, Ryan KW, Portner A, Doherty PC: Virus-specific CD8+ T-cell memory determined by clonal burst size. Nature 1994;369: 652.

    Article  PubMed  CAS  Google Scholar 

  69. Beverley PCL: Is T-cell memory maintained by crossreactive stimulation? Immunol Today 1990;11: 203.

    Article  PubMed  CAS  Google Scholar 

  70. Mackay CR, Marston WL, Dudler L: Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med 1990;171: 801.

    Article  PubMed  CAS  Google Scholar 

  71. Stout RD, Suttles J: T cells bearing the CD44hi ‘memory’ phenotype display characteristics of activated cells in G1 stage of cell cycle. Cell Immunol 1992;141:433.

    Article  PubMed  CAS  Google Scholar 

  72. Schittek B, Rajewski K: Maintenance of B-cell memory by long-lived cells generated from proliferating precursons. Nature 1990;346: 749.

    Article  PubMed  CAS  Google Scholar 

  73. Bell EB, Sparshott SM: Interconversion of CD45R subsets of CD4 T cells in vivo. Nature 1990;348:163.

    Article  PubMed  CAS  Google Scholar 

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This work was supported by grants CA38355, CA25803, and AI21487 from the United States Public Health Service. Dr. Tough is the recipient of a fellowship from the Medical Research Council of Canada. Publication No. 8855-IMM from the Scripps Research Institute.

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Tough, D.F., Sprent, J. Lifespan of lymphocytes. Immunol Res 14, 1–12 (1995). https://doi.org/10.1007/BF02918494

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