Skip to main content
SpringerLink
Log in
Book cover

Molecular Analysis of B Lymphocyte Development and Activation pp 1–14Cite as

Gene Regulatory Networks Orchestrating B Cell Fate Specification, Commitment, and Differentiation

  • Chapter

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

Abstract

The B cell developmental pathway represents a leading system for the analysis of regulatory circuits that orchestrate cell fate specification, commitment, and differentiation. We review the progress that has been achieved in the identification and characterization of regulatory components of such circuits, including transcription factors, chromatin modifying proteins, and signaling molecules. A comprehensive developmental model is proposed that invokes sequentially acting regulatory networks which dictate the generation of B cells from multipotential hematopoietic progenitors.

This is a preview of subscription content, 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adolfsson J et al (2001) Upregulation of Flt3 expression within the bone marrow Lin-Sca1+c-kit+ stem cell compartment is accompanied by loss of self-renewal capacity. Immunity 15:659–669

    Article  PubMed  CAS  Google Scholar 

  • Borge OJ et al (1999) Lymphoid-restricted development from multipotent candidate murine stem cells: distinct and complimentary functions of the c-kit and flt3 ligands. Blood 94:3781–3790

    PubMed  CAS  Google Scholar 

  • Chen CZ et al (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86

    Article  PubMed  CAS  Google Scholar 

  • Chevillard C et al (2002) A three-megabase yeast artificial chromosome contig spanning the C57BL mouse Igh locus. J Immunol 168:5659–5666

    PubMed  CAS  Google Scholar 

  • Chowdhury D, Sen R (2001) Stepwise activation of the immunoglobulin mu heavy chain gene locus. EMBO J 20:6394–6403

    Article  PubMed  CAS  Google Scholar 

  • Chowdhury D, Sen R (2003) Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements. Immunity 18:229–241

    Article  PubMed  CAS  Google Scholar 

  • DeKoter RP, Lee HJ, Singh H (2002) PU1 regulates expression of the interleukin-7 receptor in lymphoid progenitors. Immunity 16:297–309

    Article  PubMed  CAS  Google Scholar 

  • Fuxa M et al (2004) Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. Genes Dev 18:411–422

    Article  PubMed  CAS  Google Scholar 

  • Georgopoulos K et al (1994) The Ikaros gene is required for the development of all lymphoid lineages. Cell 79:143–156

    Article  PubMed  CAS  Google Scholar 

  • Goebel P et al (2001) Localized gene-specific induction of accessibility to V(D)J recombination induced by E2A and early B cell factor in nonlymphoid cells. J Exp Med 194:645–656

    Article  PubMed  CAS  Google Scholar 

  • Hagman J et al (1991) Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression. Genes Dev 7:760–773

    Google Scholar 

  • Hardy RR et al (1991) Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J Exp Med 173:1213–225

    Article  PubMed  CAS  Google Scholar 

  • Hesslein DGT et al (2003) Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segments. Genes Dev 17:37–42

    Article  PubMed  CAS  Google Scholar 

  • Igarashi H et al (2002) Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow. Immunity 17:117–130

    Article  PubMed  CAS  Google Scholar 

  • Johnson K et al (2003) Changes in histone acetylation are associated with differences in accessibility of V(H) gene segments to V-DJ recombination during B-cell ontogeny and development. Mol Cell Biol 23:2438–2450

    Article  PubMed  CAS  Google Scholar 

  • Johnson K et al B (2004) Cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5. Nat Immunol 5:853–861

    Article  PubMed  CAS  Google Scholar 

  • Kosak ST et al (2002) Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 296:158–162

    Article  PubMed  CAS  Google Scholar 

  • Li YS, Hayakawa K, Hardy RR (1993) The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver. J Exp Med 178:951–960

    Article  PubMed  CAS  Google Scholar 

  • Lin H, Grosschedl R (1995) Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature 376:263–267

    Article  PubMed  CAS  Google Scholar 

  • Liu P et al (2003) Bcl11a is essential for normal lymphoid development. Nat Immunol 4:525–532

    Article  PubMed  CAS  Google Scholar 

  • Lu R et al (2003) IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development. Genes Dev 17:1703–1708

    Article  PubMed  CAS  Google Scholar 

  • Mackarenhtschian K et al (1995) Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors. Immunity 3:147–161

    Article  Google Scholar 

  • Medina KL, Kincade PW (1994) Pregnancy-related steroids are potential negative regulators of B lymphopoiesis. Proc Natl Acad Sci U S A 91:5382–5386

    Article  PubMed  CAS  Google Scholar 

  • Medina KL et al (2001) Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen. Nat Immunol 2:718–24

    Article  PubMed  CAS  Google Scholar 

  • Medina KL et al (2004) Assembling a gene regulatory network for specification of the B cell fate. Dev Cell (in press)

    Google Scholar 

  • Mikkola I et al (2002) Reversion of B cell commitment upon loss of Pax5 expression. Science 297:110–113

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto T et al (2002) Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev Cell 3:137–147

    Article  PubMed  CAS  Google Scholar 

  • Montecino-Rodriguez, Leathers EH, Dorshkind K (2001) Bipotential B-macrophage progenitors are present in adult bone marrow. Nat Immunol 2:83–88

    Article  PubMed  CAS  Google Scholar 

  • Murre C, McCaw PS, Baltimore D (1989) A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell 56:777–783

    Article  PubMed  CAS  Google Scholar 

  • Nichogiannopoulou A et al (1999) Defects in hemopoietic stem cell activity in Ikaros mutant mice. J Exp Med 190:1201–1214

    Article  PubMed  CAS  Google Scholar 

  • Nutt SL et al (1997) Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus. Genes Dev 11:476–491

    PubMed  CAS  Google Scholar 

  • Nutt SL et al (1999) Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 401:556–562

    Article  PubMed  CAS  Google Scholar 

  • Nutt SL et al (2001) Pax5 determines the identity of B cells from the beginning to the end of B-lymphopoiesis. Int Rev Immunol 20:65–82

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Peschon JJ et al (1994) Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 180:1955–1960

    Article  PubMed  CAS  Google Scholar 

  • Quong MW, Romanow WJ, Murre C (2002) E protein function in lymphocyte development. Annu Rev Immunol 20:301–322

    Article  PubMed  CAS  Google Scholar 

  • Romanow WJ et al (2000) E2A and EBF act in synergy with the V(D)J recombinase to generate a diverse immunoglobulin repertoire in nonlymphoid cells. Mol Cell 5:343–353

    Article  PubMed  CAS  Google Scholar 

  • Saiki Y et al (2000) Human EVI9, a homologue of the mouse myeloid leukemia gene, is expressed in the hematopoietic progenitors and down-regulated during myeloid differentiation of HL60 cells. Genomics 70:387–391

    Article  PubMed  CAS  Google Scholar 

  • Saisanit S, Sun XH (1995) A novel enhancer, the pro-B enhancer, regulates Id1 gene expression in progenitor B cells. Mol Cell Biol 15:1513–1521

    PubMed  CAS  Google Scholar 

  • Saisanit S, Sun XH (1997) Regulation of the pro-B-cell-specific enhancer of the Id1 gene involves the C/EBP family of proteins. Mol Cell Biol 17:844–850

    PubMed  CAS  Google Scholar 

  • Satterwhite E et al (2001) The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. Blood 98:3413–3420

    Article  PubMed  CAS  Google Scholar 

  • Schatz DG, Oettinger MA, Schlissel MS (1992) V(D)J recombination: molecular biology and regulation. Annu Rev Immunol 10:359–383

    PubMed  CAS  Google Scholar 

  • Scott EW et al (1994) Requirement of transcription factor PU1 in the development of multiple hematopoietic lineages. Science 265:1573–1577

    PubMed  CAS  Google Scholar 

  • Seet CS, Brumbaugh RL, Kee BL (2004) Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A. J Exp Med 199:1689–1700

    Article  PubMed  CAS  Google Scholar 

  • Sitnicka, E 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. 17:463–472

    Article  PubMed  CAS  Google Scholar 

  • Sitnicka E et al (2003) Complementary signaling through flt3 and interleukin-7 receptor alpha is indispensable for fetal and adult B cell genesis. J Exp Med 198:1495–1506

    Article  PubMed  CAS  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 for E-proteins and autoregulation in the control of EBF expression. J Immunol 169:261–270

    PubMed  CAS  Google Scholar 

  • Su IH et al (2003) Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol 4:124–131

    Article  PubMed  CAS  Google Scholar 

  • Sun XH (1994) Constitutive expression of the Id1 gene impairs mouse B cell development. Cell 79:893–900

    Article  PubMed  CAS  Google Scholar 

  • Sun XH, Baltimore D (1991) An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers. Cell 64:459–470

    Article  PubMed  CAS  Google Scholar 

  • Sun XH et al (1991) Id proteins Id1 and Id2 selectively inhibit DNA binding by one class of helix-loop-helix proteins. Mol Cell Biol 11:5603–5611

    PubMed  CAS  Google Scholar 

  • Terskikh AV et al (2003) Gene expression analysis of purified hematopoietic stem cells and committed progenitors. Blood 102:94–110

    Article  PubMed  CAS  Google Scholar 

  • Vosshenrich CA et al (2003) Thymic stromal-derived lymphopoietin distinguishes fetal from adult B cell development. Nat Immunol 4:773–779

    Article  PubMed  CAS  Google Scholar 

  • Wiesmann A et al (2000) Expression of CD27 on murine hematopoietic stem and progenitor cells. Immunity 12:193–199

    Article  PubMed  CAS  Google Scholar 

  • Xie H et al (2004) Stepwise reprogramming of B cells into macrophages. Cell 117:663–676

    Article  PubMed  CAS  Google Scholar 

  • Zhuang Y Soriano P, Weintraub H (1994) The helix-loop-helix gene E2A is required for B cell formation. Cell 79:875–884

    Article  PubMed  CAS  Google Scholar 

  • Zhuang Y et al (2004) Regulation of E2A gene expression in B-lymphocyte development. Mol Immunol 40:1165–1177

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, 60637, USA

    K. L. Medina & H. Singh

Authors
  1. K. L. Medina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Singh
    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

Medina, K.L., Singh, H. (2005). Gene Regulatory Networks Orchestrating B Cell Fate Specification, Commitment, and Differentiation. 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_1

Download citation

Publish with us

Policies and ethics

Search

Navigation