Skip to main content
SpringerLink
Log in

Helix-Loop-Helix Proteins in Lymphocyte Lineage Determination

  • Chapter
Molecular Analysis of B Lymphocyte Development and Activation

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 290))

Abstract

The cells of the lymphoid system develop from multipotent hematopoietic stem cells through a series of intermediate progenitors with progressively restricted developmental options. Commitment to a given lymphoid lineage appears to be controlled by numerous transcriptional regulatory proteins that activate lineage-specific gene expression programs and extinguish expression of lineage-inappropriate genes. In this review I discuss the function of transcription factors belonging to the helix-loop-helix protein family in the control of lymphoid cell fate decisions. A model of lymphocyte lineage determination based on the antagonistic activity of transcriptional activating and repressing helix-loop-helix proteins is presented.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Akashi K, Traver D, Miyamoto T, Weissman IL (2000) A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 104:193–197

    Article  Google Scholar 

  • Allman D, Aster JC, Pear WS (2002) Notch signaling in hematopoiesis and early lymphocyte development. Immunol Rev 187:75–86

    Article  PubMed  CAS  Google Scholar 

  • Bain G, Gruenwald S, Murre C (1993) E2A, E2-2 are subunits of B-cell-specific E2-box DNA-binding proteins. Mol Cell Biol 13:3522–3529

    PubMed  CAS  Google Scholar 

  • Bain G, Robanus Maandag EC, Izon DJ, Amsen D, Kruisbeek AM, Weintraub BC, Krop I, Schlissel MS, Feeney AJ, van Roon M, van der Valk M, te Riele HPJ, Berns A, Murre C (1994) E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell 19:885–892

    Article  Google Scholar 

  • Bain G, Engel I, Robanus Maandag EC, te Riele HPJ, Voland JR, Sharp LL, Chun J, Huey B, Pinkel D, Murre C (1997) E2A deficiency leads to abnormalities in αβ T-cell development and to rapid development of T-cell lymphomas. Mol Cell Biol 17:4782–4791

    PubMed  CAS  Google Scholar 

  • Bain G, Cravatt CB, Loomans C, Alberola-Ila J, Hedrick SM, Murre C (2001) Regulation of the helix-loop-helix proteins, E2A, Id3, by the Ras-ERK MAPK cascade. Nature Immunol 1:165–171

    Article  Google Scholar 

  • Bhatia M, Bonnet D, Wu D, Murdoch B, Wrana JL, Gallacher L, Dick JE (1999) Bone morphogenetic proteins regulate the developmental program of human hematopoietic stem cells. J Exp Med 189:1139–1147

    Article  PubMed  CAS  Google Scholar 

  • Chu K, Nemoz-Gaillard E, Tsai MJ (2001) BETA2 and pancreatic islet development. Recent Prog Horm Res 16:23–46

    Article  Google Scholar 

  • Engel I, Johns C, Bain G, Rivera RR, Murre C (2001) Early thymocyte development is regulated by modulation of E2A protein activity. J Exp Med 194:733–745

    Article  PubMed  CAS  Google Scholar 

  • Fisher A, Caudy M (1998a) The function of hairy-related bHLH repressor proteins in cell fate decisions. Bioessays 10:298–306

    Article  Google Scholar 

  • Fisher AL, Caudy M (1998b) Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and inverterates. Genes Dev 12:1931–1940

    PubMed  CAS  Google Scholar 

  • Fukuyama S, Hiroi T, Yokota Y, Rennert PD, Yanagita M, Kinoshita N, Terawaki S, Shikina T, Yamamoto M, Kurono Y, Kiyono H (2002) Initiation of NALT organogenesis is independent of the IL-7R, LTbetaR, and NIK signaling pathways but requires the Id2 gne and CD3(−)CD4(+)CD45(+) cells. Immunity 17:31–40

    Article  PubMed  CAS  Google Scholar 

  • Garrell J, Campuzano S (1991) The helix-loop-helix domain: a common motif for bristles, muscles and sex. Bioessays 13:493–498

    Article  PubMed  CAS  Google Scholar 

  • Hacker C, Kirsch RD, Ju XS, Hieronymus T, Gust TC, Kuhl C, Jorgas T, Kurz SM, Rose-John S, Yokota Y, Zenke M (2003) Transcriptional profiling identifies Id2 function in dendritic cell development. Nat Immunol 1:380–386

    Article  Google Scholar 

  • Hagman J, Belanger C, Travis A, Turck CW, Grosschedl R (1993) Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression. Genes Dev 1:760–773

    Google Scholar 

  • Hagman J, Gutch MJ, Lin H, Grosschedl R (1995) EBF contains a novel zinc coordination motif and multiple dimerization and transcriptional activation domains. EMBO J 14:2907–2916

    PubMed  CAS  Google Scholar 

  • Hardy RR, Carmack CE, Shinton SA, Kemp JD, Hayakawa K (1991) Resolution and characterization of pro-B, pre-pro-B cell stages in normal mouse bone marrow. J Exp Med 173:1213–1225

    Article  PubMed  CAS  Google Scholar 

  • Heemskerk MHM, Blom B, Nolan G, Stegmann APA, Bakker AQ, Weirer K, Res PCM, Spits H (1997) Inhibition of T cell and promotion of natural killer cell development by the dominant negative helix loop helix factor IdJ. Exp Med 186:1597–1602

    Article  CAS  Google Scholar 

  • Helms AW, Johnson JE (2003) Specification of dorsal spinal cord interneurons. Curr Opin Neurobiol 13:42–49

    Article  PubMed  CAS  Google Scholar 

  • Ikawa T, Fujimoto S, Kawamoto H, Katsura Y, Yokota Y (2001) Commitment to natural killer cells requires the helix-loop-helix inhibitor Id. Proc Natl Acad Sci 18:5164–5169

    Article  Google Scholar 

  • Kee BL, Murre C (1998) Induction of early B cell factor (EBF) and multiple B lineage genes by the basic helix-loop-helix transcription factor EJ. Exp Med 188:699–713

    Article  CAS  Google Scholar 

  • Kee BL, Rivera RR, Murre C (2001) Id3 inhibits B lymphocyte progenitor growth and survival in response to TGF-β. Nature Immunol 1:242–247

    Article  Google Scholar 

  • Kee BL, Bain G, Murre C (2002) IL7Rα and E47: independent pathways required for the development of multipotent lymphoid progenitors. EMBO J 21:103–113

    Article  PubMed  CAS  Google Scholar 

  • Kim D, Peng XC, Sun X-H (1999) Massive apoptosis of thymocytes in T-cell-deficient Id1 transgenic mice. Mol Cell Biol 19:8240–8253

    PubMed  CAS  Google Scholar 

  • Kim D, Xu M, Nie L, Peng XC, Jimi E, Voll RE, Nguyen T, Ghosh S, Sun X-H (2002) Helix-loop-helix proteins regulate pre-TCR, TCR signaling through modulation of Rel/NF-kappaB activities. Immunity 16:9–21

    Article  PubMed  CAS  Google Scholar 

  • Lin H, Grosschedl R (1995) Failure of B-cell differentiation in mice lacking the transcription factor EBF Nature 176:263–267

    Google Scholar 

  • Massari ME, Murre C (2000) Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol 10:429–440

    Article  Google Scholar 

  • Mebius RE (2003) Organogenesis of lymphoid tissues. Nat Rev Immunol 1:292–303

    Article  Google Scholar 

  • Mebius RE, Miyamoto T, Christensen J, Domen J, Cupedo T, Weissman IL, Akashi K (2001) The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+CD4+CD3− cells, as well as macrophages. J Immunol 166:6593–6601

    PubMed  CAS  Google Scholar 

  • Murre C, Baltimore D (1992)The helix-loop-helix motif: structure and function. In: McKnight SL, Yamamoto KR (eds) Transcriptional regulation. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 161–879

    Google Scholar 

  • Murre C, McCaw PS, Baltimore D (1989) A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, myc proteins. Cell 16:777–783

    Article  Google Scholar 

  • O'Riordan M, Grosschedl R (1999) Coordinate regulation of B cell differentiation by the transcription factors EBF, E2A Immunity 11:21–31

    Google Scholar 

  • Pan L, Sato S, Frederick JP, Sun X-H, Zhuang Y (1999) Impaired immune responses and B-cell proliferation in mice lacking the Id3 gene. Mol Cell Biol 19:5969–5980

    PubMed  CAS  Google Scholar 

  • Pierelli L, Marone M, Baonanno G, Rutella S, de Ritis D, Mancuso S, Leone G, Scambia G (2002) Transforming growth factor-beta 1 causes transcriptional activation of CD34 and preserves haematopoietic stem/progenitor cell activity. Br J Haematol 118:627–637

    Article  PubMed  CAS  Google Scholar 

  • Prohaska SS, Scherer DC, Weissman IL, Kondo M (2002) Developmental plasticity of lymphoid progenitors. Semin Immunol 14:377–384

    Article  PubMed  CAS  Google Scholar 

  • Rivera RR, Murre C (2001) The regulation and function of the Id proteins in lymphocyte development. Oncogene 10:8308–8316

    Article  Google Scholar 

  • Rivera RR, Johns CP, Quan J, Johnson RS, Murre C (2000) Thymocyte selection is regulated by the helix-loop-helix inhibitor protein Id. Immunity 12:17–26

    Article  PubMed  CAS  Google Scholar 

  • Sabourin LA, Rudnicki MA (2000) The molecular regulation of myogenesis. Clin Genet 17:16–25

    Article  Google Scholar 

  • Sasai Y, Kageyama R, Tagawa Y, Shigemoto R, Nakanishi S (1992) Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and enhancer of split. Genes Dev 1:2620–2634

    Google Scholar 

  • Shen C-P, Kadesch T (1995) B-cell-specific DNA binding by an E47 homodimer. Mol Cell Biol 15:4518–4524

    PubMed  CAS  Google Scholar 

  • Sigvardsson M, O'Riordan M, Grosschedl R (1997) EBF, E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. Immunity 1:25–36

    Article  Google Scholar 

  • Sigvardsson M, Clark DR, Fitzsimmons D, Doyle M, Akerblad P, Breslin T, Bilke S, Li R, Yeamans C, Zhang G, Hagman J (2002) Early B-cell factor, E2A, and Pax-5 cooperate to activate the early B cell-specific mb-1 promoter. Mol Cell Biol 12:8539–8551

    Article  Google Scholar 

  • Smith EM, Gisler R, Sigvardsson M (2002) Cloning and characterization of a promoter flanking the early B cell factor (EBF) gene indicates roles of E-proteins and autoregulation in the control of EBF expression. J Immunol 169:261–270

    PubMed  CAS  Google Scholar 

  • Timita K, Hattori M, Nakamura E, Nakanishi S, Minato N, Kageyama R (1999) The bHLH gene Hes1 is essential for expansion of early T cell precursors. Genes Dev 13:1203–1210

    Google Scholar 

  • Tudor K-SRS, Payne KJ, Yamashita Y, Kincade PW (2000) Functional assessment of precursors from murine bone marrow suggests a sequence of early B lineage differentiation events. Immunity 12:335–345

    Article  PubMed  CAS  Google Scholar 

  • Van Doren M, Ellis HM, Posakony JW (1991) The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless/achaetescute protein complexes. Development 113:245–255

    PubMed  Google Scholar 

  • Yan W, Young AZ, Soares VC, Kelley R, Benezra R, Zhuang Y (1997) High incidence of T-cell tumors in E2A-null mice and E2A/Id1 double-knockout mice. Mol Cell Biol 17:7317–7327

    PubMed  CAS  Google Scholar 

  • Yang D, Lu H, Hong Y, Jinks TM, Estes PA, Erickson JW (2001) Interpretation of X chromosome dose at Sex-lethal requires non-E-box sites for the basic helix-loop-helix proteins SISB, daughterless. Mol Cell Biol 11:1581–1592

    Article  Google Scholar 

  • Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nishikawa S, Gruss P (1999) Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id. Nature 197:702–706

    Article  Google Scholar 

  • Yokota Y, Mori S, Nishikawa S-I, Mansouri A, Gruss P, Kusunoki T, Katakai T, Shimizu A (2002) The helix-loop-helix inhibitor Id2 and cell differentiation control. Curr Top Microbiol Immunol 151:35–41

    Google Scholar 

  • Zhuang Y, Soriano P, Weintraub H (1994) The helix-loop-helix gene E2A is required for B cell formation. Cell 19:875–884

    Article  Google Scholar 

  • Zhuang Y, Cheng P, Weintraub H (1996) B-lymphocyte development is regulated by the combined dosage of three basic helix-loop-helix genes, E2A, E2-2 and HEB Mol. Cell Biol 16:2898–2905

    CAS  Google Scholar 

  • Zhuang Y, Barndt RJ, Pan L, Kelley R, Dai M (1998) Functional replacement of the mouse E2A gene with a human HEB cDNA Mol. Cell Biol 18:3340–3349

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Chicago, MC1089, 5841 S. Maryland Ave., Chicago, IL, 60637, USA

    B. L. Kee

Authors
  1. B. L. Kee
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Molecular Genetics and Cell Biology Howard Hughes Medical Institute, The University of Chicago, 5841 S. Maryland Ave. N112, Chicago, IL, 60637, USA

    Harinder Singh

  2. Department of Cellular and Molecular Immunology, Max-Plank-Institute of Immunobiology, Stübeweg 51, 79108, Freiburg, Germany

    Rudolf Grosschedl

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag

About this chapter

Cite this chapter

Kee, B.L. (2005). Helix-Loop-Helix Proteins in Lymphocyte Lineage Determination. In: Singh, H., Grosschedl, R. (eds) Molecular Analysis of B Lymphocyte Development and Activation. Current Topics in Microbiology and Immunology, vol 290. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26363-2_2

Download citation

Publish with us

Policies and ethics

Search

Navigation