Advertisement

Immunologic Research

, 40:193 | Cite as

Extrinsic and intrinsic regulation of early natural killer cell development

  • Markus D. Boos
  • Kevin Ramirez
  • Barbara L. KeeEmail author
Article

Abstract

Natural killer (NK) cells are lymphocytes that play a critical role in both adaptive and innate immune responses. These cells develop from multipotent progenitors in the embryonic thymus and neonatal or adult bone marrow and recent evidence suggests that a subset of these cells may develop in the thymus. Thymus- and bone marrow-derived NK cells have unique phenotypes and functional abilities supporting the hypothesis that the microenvironment dictates the outcome of NK cell development. A detailed understanding of the mechanisms controlling this developmental program will be required to determine how alterations in NK cell development lead to disease and to determine how to harness this developmental program for therapeutic purposes. In this review, we discuss some of the known extrinsic stromal-cell derived factors and cell intrinsic transcription factors that function in guiding NK cell development.

Keywords

NK cells Transcription factors Cytokines Stromal cell Lineage commitment 

Notes

Acknowledgements

We thank the members of our laboratory and Stephen Nutt for insightful discussion and helpful comments on this manuscript. Work from our lab was supported by the National Institutes of Health/National Cancer Institute R01 CA099978.

References

  1. 1.
    Lanier LL. NK cell recognition. Ann Rev Immunol 2005;23:225–74.Google Scholar
  2. 2.
    Yokoyama WM. Natural killer cell immune responses. Immunol Rev 2005;32:317–25.Google Scholar
  3. 3.
    Orange JS. Human natural killer cell deficiencies. Curr Opin Allergy Clin Immunol 2006;6:399–409.PubMedCrossRefGoogle Scholar
  4. 4.
    Suzuki R, Nakamura S. Malignancies of natural killer (NK) cell precursor: myeloid/NK cell precursor acute leukemia and blastic NK cell lymphoma/leukemia. Leuk Res 1999;23:615–24.PubMedGoogle Scholar
  5. 5.
    Suzuki R, Suzumiya J, Nakamura S, et al. Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia 2004;18:763–70.PubMedGoogle Scholar
  6. 6.
    Kondo M, Weissman IL, Akashi K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 1997;91:661–72.PubMedGoogle Scholar
  7. 7.
    Kouro T, Kumar V, Kincade PW. Relationships between early B- and NK-lineage lymphocyte precursors in bone marrow. Blood 2002;100:3672–80.PubMedGoogle Scholar
  8. 8.
    Welner RS, Pelayo R, Garrett KP, et al. Interferon-producing killer dendritic cells (IKDCs) arise via a unique differentiation pathway from primitive c-kitHiCD62L+ lymphoid progenitors. Blood 2007;109:4825–931.PubMedGoogle Scholar
  9. 9.
    DiSanto JP, Vosshenrich CA. Bone marrow versus thymic pathways of natural killer cell development. Immunol Rev 2006;214:35–46.Google Scholar
  10. 10.
    Nutt SL, Kee BL. The transcriptional regulation of B-cell lineage commitment. Immunity 2007;26:715–25.PubMedGoogle Scholar
  11. 11.
    Rothenberg EV. Negotiation of the T lineage fate decision by transcription-factor interplay and microenvironmental signals. Immunity 2007;26:690–702.PubMedGoogle Scholar
  12. 12.
    Singh H, Medina KL, Pongubala JM. Contingen gene regulatory networks and B cell fate specification. Proc Natl Acad Sci USA 2005;102:4949–53.PubMedGoogle Scholar
  13. 13.
    DiSanto JP. Natural killer cell developmental pathways: a question of balance. Annu Rev Immunol 2006;24:257–86.Google Scholar
  14. 14.
    Yokoyama WM, Kim S, French AR. The dynamic life of natural killer cells. Ann Rev Immunol 2004;22:405–29.Google Scholar
  15. 15.
    Freud AG, Yokohama A, Becknell B, et al. Evidence for discrete stages of human natural killer cell differentiation in vivo. J Exp Med 2006;203:1033–43.PubMedGoogle Scholar
  16. 16.
    Adolfsson J, Borge OJ, Bryder D, et al. Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity 2001;15:659–69.PubMedGoogle Scholar
  17. 17.
    Adolfsson J, Mansson R, Buza-Vidas N, et al. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential: a revised road map for adult blood lineage commitment. Cell 2005;121:295–306.PubMedGoogle Scholar
  18. 18.
    Kim S, Iizuka K, Kang HS, et al. In vivo developmental stages in murine natural killer cell maturation. Nat Immunol 2002;3:523–28.PubMedGoogle Scholar
  19. 19.
    Rosmaraki EE, Douagi I, Roth C, et al. Identification of committed NK cell progenitors in adult murine bone marrow. Eur J Immunol 2001;31:1900–9.PubMedGoogle Scholar
  20. 20.
    Vosshenrich CA, Ranson T, Samson SI, et al. Roles for common cytokine receptor gamma-chain-dependent cytokines in the generation, differentiation, and maturation of NK cell precursors and peripheral NK cells in vivo. J Immunol 2005;174:1213–21.PubMedGoogle Scholar
  21. 21.
    McNerney ME, Kumar V. The CD2 family of natural killer cell receptors. Curr Top Microbiol Immunol 2006;298:91–120.PubMedGoogle Scholar
  22. 22.
    Raulet DH. Roles of the NKG2D immunoreceptor and its ligands. Nat Rev Immunol 2003;3:781–90.PubMedGoogle Scholar
  23. 23.
    Taniguchi RT, Guzior D, Kumar V. 2B4 inhibits NK cell fratricide. Blood 2007;110:2020–3.PubMedGoogle Scholar
  24. 24.
    Rouhi A, Gagnier L, Takei F, et al. Evidence for epigenetic maintenance of Ly49a monoallelic gene expression. J Immunol 2006;176:2991–9.PubMedGoogle Scholar
  25. 25.
    Tanamachi DM, Moniot DC, Cado D, et al. Genomic Ly49A transgenes: basis of variegated Ly49A gene expression and identification of a critical regulatory element. J Immunol 2004;172:1074–82.PubMedGoogle Scholar
  26. 26.
    Saleh A, Davies GE, Pascal V, et al. Identification of probabilistic transcriptional switches in the L49 gene cluster: a eukaryotic mechanism for selective gene activation. Immunity 2004;21:55–66.PubMedGoogle Scholar
  27. 27.
    Yokoyama WM, Kim S. Licensing of natural killer cells by self-major histocompatibility complex class I. Immunol Rev 2006;214:143–54.PubMedGoogle Scholar
  28. 28.
    Takeda K, Cretney E, Hayakawa Y, et al. TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver. Blood 2005;105:2082–89.PubMedGoogle Scholar
  29. 29.
    Zamai L, Ahmad M, Bennett IM, et al. Natural killer (NK) cell-mediated cytotoxicity:differential use of TRAIL and Fas ligand by immature and mature primary human NK cells. J Exp Med 1998;188:2375–80.PubMedGoogle Scholar
  30. 30.
    Samson SI, Richard O, Tavian M, et al. Gata-3 promotes maturation, IFN-gamma production, and liver-specific homing of NK cells. Immunity 2003;19:701–11.PubMedGoogle Scholar
  31. 31.
    Vosshenrich CA, Garcia-Ojeda ME, Samson-Villeger SI, et al. A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127. Nat Immunol 2006;7:1217–24.PubMedGoogle Scholar
  32. 32.
    Stewart CA, Xalzer T, Robbins SH, et al. Germ-line and rearranged Tcrd transcription distinguish bona fide NK cells and NK-like gammadelta T cells. Eur J Immunol 2007;37:1442–52.PubMedGoogle Scholar
  33. 33.
    Freud AG, Caligiuri MA. Human natural killer cell development. Immunol Rev 2006;214:56–72.PubMedGoogle Scholar
  34. 34.
    Allman D, Sambandam A, Kim S, et al. Thymopoiesis independent of common lymphoid progenitors. Nat Immunol 2003;4:168–74.PubMedGoogle Scholar
  35. 35.
    Schmitt TM, Ciofani M, Petrie HT, et al. Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions. J Exp Med 2004;200:469–79.PubMedGoogle Scholar
  36. 36.
    Godin I, Cumano A. The hare and the tortoise: an embryonic haematopoietic race. Nat Rev Immunol 2002;2:166–71.Google Scholar
  37. 37.
    Carlyle JR, Zuniga-Pflucker JC. Lineage commiment and differentiation of T and natural killer lymphocytes in the fetal mouse. Immunol Rev 1998;165:63–74.PubMedGoogle Scholar
  38. 38.
    Rodewald H-R, Moingeon P, Lucich JL, et al. A population of early fetal thymocytes expressing FcγRII/III contains precursors of T lymphocytes and natural killer cells. Cell 1992;69:139–50.PubMedGoogle Scholar
  39. 39.
    Ikawa T, Kawamoto H, Fujimoto S, et al. Commitment of common T/Natural killer (NK) progenitors to unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor assay. J Exp Med 1999;190:1617–27.PubMedGoogle Scholar
  40. 40.
    Carlyle JR, Michie AM, Cho SK, et al. Natural killer cell development and function precede alpha beta T cell differentiation in mouse fetal thymic ontogeny. J Immunol 1998;160:744–53.PubMedGoogle Scholar
  41. 41.
    Carlyle JR, Zunig-Pflucker JC. Regulation of NK1.1 expression during lineage commitment of progenitor thymocytes. J Immunol 1998;161:6544–51.PubMedGoogle Scholar
  42. 42.
    Rodewald H-R, Kretzschmar K, Takeda S, et al. Identification of pro-thymocytes in murine fetal blood: T lineage commitment can precede thymus colonization. EMBO J 1994;13:4229–40.PubMedGoogle Scholar
  43. 43.
    Carlyle JR, Mitchie AM, Furlonger C, et al. Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes. J Exp Med 1997;186:173–82.PubMedGoogle Scholar
  44. 44.
    Carlyle JR, Zunig-Pflucker JC. Requirement for the thymus in alpha beta T lymphocyte lineage commitment. Immunity 1998;9:187–97.PubMedGoogle Scholar
  45. 45.
    Douagi I, Colucci F, DiSanto JP, et al. Identification of the earliest prethymic bipotent T/NK progenitor in murine fetal liver. Blood 2002;99:463–71.PubMedGoogle Scholar
  46. 46.
    Sivakumar PV, Bennett M, Kumar V. Fetal and neonatal NK1.1+ Ly-49- cells can distinguish between major histocompatibility complex class I(hi) and classI(lo) target cells: evidence for a Ly-49-independent negative signaling receptor. Eur J Immunol 1997;27:3100–4.PubMedGoogle Scholar
  47. 47.
    Sivakumar PV, Gunturi A, Salcedo M, et al. Expression of functional CD94/NKG2A inhibitory receptors on fetal NK1.1+Ly-49- cells: a possible mechanism of tolerance during NK cell development. J Immunol 1999;162:6976–80.PubMedGoogle Scholar
  48. 48.
    Haller O, Wigzell H. Suppression of natural killer cell activity with radioactive strontium: effector cells are marrow dependent. J Immunol 1977;118:1503–6.PubMedGoogle Scholar
  49. 49.
    Kumar V, Ben-Ezra J, Bennett M, et al. Natural killer cells in mice treated with 89strontium:normal target-binding cell numbers but inability to kill even after interferon administration. J Immunol 1979;123:1832–8.PubMedGoogle Scholar
  50. 50.
    Puzanov IJ, Bennett M, Kumar V. IL-15 can substitute for the marrow microenvironment in the differentiation of natural killer cells. J Immunol 1996;157:4282–5.PubMedGoogle Scholar
  51. 51.
    Williams ND, Moore TA, Schatzle JD, et al. Generation of lytic natural killer 1.1+, Ly-49- cells from multipotential murine bone marrow progenitors in a stromal-free culture: definition of cytokine requirements and developmental intermediates. J Exp Med 1997;186:1609–14.PubMedGoogle Scholar
  52. 52.
    Williams NS, Klem J, Puzanov IJ, et al. Differentiation of NK1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitors. J Immunol 1999;163:2648–56.PubMedGoogle Scholar
  53. 53.
    Yu H, Fehniger TA, Fuchshuber P, et al. Flt3 ligand promotes the generation of a distinct CD34(+) human natural killer cell progenitor that responds to interleukin-15. Blood 1998;92:3647–57.PubMedGoogle Scholar
  54. 54.
    Zhang X, Sun S, Hwang I, et al. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 1998;8:591–9vuctured>PubMedGoogle Scholar
  55. 55.
    Lodolce JP, Boone DL, Chai S, et al. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 1998;9:669–76.PubMedGoogle Scholar
  56. 56.
    Kennedy MK, Park LS. Characterization of interleukin-15 (IL-15) and the IL-15 receptor complex. J Clin Immunol 1996;16:134–43.PubMedGoogle Scholar
  57. 57.
    Dubois S, Mariner J, Waldmann TA, et al. IL-15Ralpha recycles and presents IL-15 in trans to neighboring cells. Immunity 2002;17:537–47.PubMedGoogle Scholar
  58. 58.
    Burkett PR, Koka R, Chien M, et al. Coordinate expression and trans presentation of interleukin IL-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis. J Exp Med 2004;200:825–34.PubMedGoogle Scholar
  59. 59.
    Williams NS, Klem J, Puzanov IJ, et al. Natural killer cell differentiation: insights from knockout and transgenic mouse models and in vitro systems. Immunol Rev 1998;165:47–61.PubMedGoogle Scholar
  60. 60.
    Sitnicka E, Bryder D, Theilgaard-Monch K, et al. Key role of flt3 ligand in regulation of the common lymphoid progenitor but not in maintenance of the hematopoietic stem cell pool. Immunity 2002;17:463–72.PubMedGoogle Scholar
  61. 61.
    Waskow C, Paul S, Haller C, et al. Viable c-Kit (W/W) mutants reveal pivotal role for c-kit in the maintenance of lymphopoiesis. Immunity 2002;17:277–88.PubMedGoogle Scholar
  62. 62.
    Reilly JT. Receptor tyrosine kinases in normal and malignant haematopoiesis. Blood Rev 2003;17:241–8.PubMedGoogle Scholar
  63. 63.
    Scheijen B, Griffin JD. Tryosine kinase oncogenes in normal hematopoiesis and hematological disease. Oncogene 2002;21:3314–33.PubMedGoogle Scholar
  64. 64.
    Colucci F, DiSanto JP. The receptor tyrosine kinase c-kit provides a critical singal for survival, expansion, and maturation of mouse natural killer cells. Blood 2000;95:984–91.PubMedGoogle Scholar
  65. 65.
    McKenna HJ, Stocking KL, Miller RE, et al. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 2000;95:3489–97.PubMedGoogle Scholar
  66. 66.
    Cosman D. The hematopoietin receptor superfamily. Cytokine 1993;5:95–206.PubMedGoogle Scholar
  67. 67.
    Kee BL, Bain G, Murre C. IL7Ra and E47: independent pathways required for the development of multipotent lymphoid progenitors. EMBO J 2002;21:103–13.PubMedGoogle Scholar
  68. 68.
    Roth C, Rothlin C, Riou S, et al. Stromal-cell regulation of natural killer cell differentiation. J Mol Med 2007; in press.Google Scholar
  69. 69.
    Ciofani M, Zuniga-Pflucker JC. The thymus as an inductive site for T lymphopoiesis. Annu Rev Cell Dev Biol 2006; in press.Google Scholar
  70. 70.
    Pear WS, Radtke F. Notch signaling in lymphopoiesis. Semin Immunol 2003;15:69–79.PubMedGoogle Scholar
  71. 71.
    DeHart SL, Heikens MJ, Tsai S. Jagged2 promotes the development of natural killer cells and the establishment of functional natural killer cell lines. Blood 2005;105:3521–7.PubMedGoogle Scholar
  72. 72.
    Jaleco AC, Neves H, Hooijberg E, et al. Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation. J Exp Med 2001;194:991–1002.PubMedGoogle Scholar
  73. 73.
    Lehar SM, Dooley J, Farr AG, et al. Notch ligands Delta1 and Jagged1 transmit distinct signals to T-cell precursors. Blood 2005;105:1440–7.PubMedGoogle Scholar
  74. 74.
    Schmitt TM, Zuniga-Pflucker JC. Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro. Immunity 2002;17:749–56.PubMedGoogle Scholar
  75. 75.
    Carotta S, Brady J, Wu L, et al. Transient Notch signaling induces NK cell potential in Pax5-deficient pro-B cells. Eur J Immunol 2006;36:3294–304.PubMedGoogle Scholar
  76. 76.
    Rolink AG, Balciunaite G, Demoliere C, et al. The potential involvement of Notch signaling in NK cell development. Immunol Lett 2006;107:50–7.PubMedGoogle Scholar
  77. 77.
    Yang LT, Nichols JT, Yao C, et al. Fringe glycosyltransferases differentially modulate Notch1 proteolysis induced by Delta1 and Jagged1. Mol Biol Cell 2005;16:927–42.PubMedGoogle Scholar
  78. 78.
    Norris PS, Ware CF. The LT beta R signaling pathway. Adv Exp Med Biol 2007;597:160–72.PubMedCrossRefGoogle Scholar
  79. 79.
    Iizuka K, Chaplin DD, Wang Y, et al. Requirement for membrane lymphotoxin in natural killer cell development. Proc Natl Acad Sci USA 1999;96:6336–40.PubMedGoogle Scholar
  80. 80.
    Wu Q, Sun Y, Wang J, et al. Signal via lymphotoxin-beta R on bone marrow stromal cells is required for an early checkpoint of NK cell development. J Immunol 2001;166:1684–9.PubMedGoogle Scholar
  81. 81.
    Lian RH, Chin RK, Nemeth HE, et al. A role for lymphotoxin in the acquisition of Ly49 receptors during NK cell development. Eur J Immunol 2004;34:2699–707.PubMedGoogle Scholar
  82. 82.
    Dittmer J. The biology of the Ets1 proto-oncogene. Mol Cancer 2003;10:1–29.Google Scholar
  83. 83.
    Barton K, Muthusamy N, Fischer C, et al. The Ets-1 transcription factor is required for the development of natural killer cells in mice. Immunity 1998;9:555–63.PubMedGoogle Scholar
  84. 84.
    Ye SK, Kim TJ, Won SS, et al. Transcriptional regulation of the mouse interleukin-2 receptor beta chain gene by Ets and Erg-1. Biochem Biophys Res Commun 2005;329:1094–101.PubMedGoogle Scholar
  85. 85.
    Grund EM, Spyropoulos DD, Watson DK, et al. Interleukins 2 and 15 regulate Ets1 expression via ERK1/2 and MNK1 in human natural killer cells. J Biol Chem 2005;280:4772–8.PubMedGoogle Scholar
  86. 86.
    Foulds CE, Nelson ML, Blaszczak AG, et al. Ras/mitogen-activated protein kinase signaling activates Ets-1 and Ets-2 by CBP/p300 recruitment. Mol Cell Biol 2004;24:10954–64.PubMedGoogle Scholar
  87. 87.
    Boos MD, Eberl G, Yokota Y, et al. Mature natural killer cell and lymphid tissue inducing cell development requires Id2-mediated suppression of E-protein activity. J Exp Med 2007;204:1119–30.PubMedGoogle Scholar
  88. 88.
    DeKoter RP, Lee HJ, Singh H. PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors. Immunity 2002;16:297–309.PubMedGoogle Scholar
  89. 89.
    Medina KL, Pongubala JM, Reddy KL, et al. Assembling a gene regulatory network for specification of the B cell fate. Dev Cell 2004;7:607–17.PubMedGoogle Scholar
  90. 90.
    Colucci F, Samson SI, DeKoter RP, et al. Differential requirement for the transcription factor PU.1 in the generation of natural killer cells versus B and T cells. Blood 2001;97:2625–32.PubMedGoogle Scholar
  91. 91.
    Lacorazza HD, Miyazaki Y, Di Cristofano A, et al. The ETS protein MEF plays a critical role in perforin gene expression and development of natural killer and NK-T cells. Immunity 2002;17:437–49.PubMedGoogle Scholar
  92. 92.
    Townsend MJ, Weinmann AS, Matsuda JL, et al. T-bet regulates the terminal maturation and homeostasis of NK and V alpha14i NKT cells. Immunity 2004;20:477–94.PubMedGoogle Scholar
  93. 93.
    Szabo SJ, Kim ST, Costa GL, et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 2000;100:655–69.PubMedGoogle Scholar
  94. 94.
    Mullen AC, High FA, Hutchins AS, et al. Role of T-bet in commitment of TH1 cells before IL-12 dependent selection. Science 2001;292:1907–10.PubMedGoogle Scholar
  95. 95.
    Hwang ES, Szabo SJ, Schwartzberg PL, et al. T helper cell fate specified by kinase-mediated interaction of T-bet with Gata3. Science 2005;307:430–3.PubMedGoogle Scholar
  96. 96.
    Usui T, Preiss, Jc, Kanno Y, et al. T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med 2006;203:755–66.PubMedGoogle Scholar
  97. 97.
    Intlekofer AM, Takemoto N, Wherry EJ, et al. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol 2005;6:1236–44.PubMedGoogle Scholar
  98. 98.
    Lohoff M, Duncan GS, Ferrick D, et al. Deficiency in the transcription factor interferon regulatory factor (IRF)-2 leads to severely compromised development of natural killer and T helper type 1 cells. J Exp Med 2000;192:325–36.PubMedGoogle Scholar
  99. 99.
    Taki S, Nakajima S, Ichikawa E, et al. IFN regulatory factor-2 deficiency revealed a novel checkpoint critical for the generation of peripheral NK cells. J Immunol 2005;174:6005–12.PubMedGoogle Scholar
  100. 100.
    Kee BL, Helix-loop-helix proteins in lymphocyte lineage determination. In: Singh H, Grosschedl R, editors. CTMI. Molecular analysis of B lymphocyte development and activation. Springer-verlag; 2005. p. 15–27.Google Scholar
  101. 101.
    Sun X-H, Copeland NG, Jenkins NA, et al. Id proteins Id1 and Id2 selectively inhibit DNA binding by one class of helix-loop-helix proteins. Mol Cell Biol 1991;11:5603–11.PubMedGoogle Scholar
  102. 102.
    Massari ME, Murre C. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol 2000;20:429–40.PubMedGoogle Scholar
  103. 103.
    Stinson J, Inoue T, Yates P, et al. Regulation of TCF ETS-domain transcription factors by helix-loop-helix motifs. Nucleic Acids Res 2003;31:4717–28.PubMedGoogle Scholar
  104. 104.
    Yates PR, Atherton GT, Deed RW, et al. Id helix-loop-helix proteins inhibit nucleoprotein complex formation by the TCF ETS-domain transcription factors. Embo J 1999;18:968–76.PubMedGoogle Scholar
  105. 105.
    Lasorella A, Noseda M, Beyna M, et al. Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins. Nature 2000;407:592–8.PubMedGoogle Scholar
  106. 106.
    Sigvardsson M, O’Riordan M, Grosschedl R. EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. Immunity 1997;7:25–36.PubMedGoogle Scholar
  107. 107.
    Seet CS, Brumbaugh RL, Kee BL. Early B-cell factor promotes B-lymphopoiesis with reduced interleukin-7-responsiveness in the absence of E2A. J Exp Med 2004;199:1689–700.PubMedGoogle Scholar
  108. 108.
    Cobaleda C, Schebesta A, Delogu A, et al. Pax5: the guardian of B cell identity and function. Nat Immunol 2007;8:463–70.PubMedGoogle Scholar
  109. 109.
    Roessler S, Gyory I, Imhof S, et al. Distinct promoters mediate the regulation of Ebf1 gene expression by interleukin-7 and Pax5. Mol Cell Biol 2007;27:579–94.PubMedGoogle Scholar
  110. 110.
    Schebesta A, McManus S, Salvagiotto G, et al. Transcription factor Pax5 activates the chromatin of key genes involved in B cell signaling, adhesion, migration, and immune function. Immunity 2007;27:49–63.PubMedGoogle Scholar
  111. 111.
    Heemskerk MHM, Blom B, Nolan G, et al. Inhibition of T cell and promotion of natural killer cell development by the dominant negative helix loop helix factor Id3. J Exp Med 1997;186:1597–602.PubMedGoogle Scholar
  112. 112.
    Bain G, Cravatt CB, Loomans C, et al. Regulation of the helix-loop-helix proteins, E2A and Id3, by the Ras-ERK MAPK cascade. Nature Immunol 2001;2:165–71.Google Scholar
  113. 113.
    Anderson MK. At the crossroads: diverse roles of early thymocyte transcriptional regulators. Immunol Rev 2006;209:191–211.PubMedGoogle Scholar
  114. 114.
    Yokota Y, Mansouri A, Mori S, et al. Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature 1999;397:702–6.PubMedGoogle Scholar
  115. 115.
    Ikawa T, Fujimoto S, Kawamoto H, et al. Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2. Proc Natl Acad Sci 2001;98:5164–9.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Markus D. Boos
    • 1
  • Kevin Ramirez
    • 1
  • Barbara L. Kee
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Committees on ImmunologyThe University of ChicagoChicagoUSA
  2. 2.Cancer BiologyThe University of ChicagoChicagoUSA
  3. 3.Developmental BiologyThe University of ChicagoChicagoUSA
  4. 4.Department of PathologyThe University of ChicagoChicagoUSA

Personalised recommendations