Transcriptional Control of B-Cell Differentiation by EBF and E2A

  • Mikael Sigvardsson
  • Rudolf Grosschedl
Part of the Contemporary Immunology book series (CONTIM)


B-cell differentiation is a complex developmental process that ultimately generates antibody-secreting plasma cells. The B-cell lineage involves multiple stages of differentiation that have been characterized by the expression of cell surface markers and the rearrangement status of the immunoglobulin (Ig) loci (Fig. 1). The earliest characterized cells that are committed to the B-cell lineage express the surface markers B220, CD43, AA4.1 and have the Ig heavy chain locus in germline configuration (1, 2). Pro-B and preB-cells express genes that are involved in the rearrangement of the Ig gene loci and signal transduction through the pre-B-cell receptor (reviewed in 3,4). In particular, these cells express the recombinase-activating genes (Rag1 and Rag2), the terminal deoxytransferase gene (TdT), the λ5 and VpreB genes encoding the Ig surrogate light chains, and the mb-1 and B29 genes encoding the Igα and Igβ proteins that mediate signaling. The pro-B- and pre-B-cells can be subdivided into populations that express different combinations of cell surface markers and may represent distinct stages of differentiation (Fig. 1) (1,5). Further differentiation generates immature B-cells that have rearranged their Ig light chain locus and have downregulated the expression of the λ5 and VpreB surrogate light genes (reviewed in ref. 6). Taken together, these early stages of B-cell differentiation represent the antigen-independent phase that occurs predominantly in the adult bone marrow. The late stages of B-cell differentiation that occur in peripheral lymphoid organs involve activation of B-cells by antigen and/or T helper cells and the generation of antibody-secreting plasma cells. These late stages of differentiation also result in somatic hypermutation of the Ig genes and antibody class switching (reviewed in ref. 7).


bHLH Protein Transcriptional Activation Domain Cell BioI Surrogate Light Chain Antibody Class Switching 
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  1. 1.
    Hardy, R., Carmack, C., Shinton, S., Kemp, J., and Hayakawa, K. (1991) Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J. Exp. Med. 173, 1213–1225.PubMedCrossRefGoogle Scholar
  2. 2.
    Li, Y.-S., Wasserman, R., Hayakawa, K., and Hardy, R. (1996) Identification of the earliest B lineage stage in mouse bone marrow. Immunity 5, 572–535.Google Scholar
  3. 3.
    Alt, F., Oltz, E., Young, F., Gorman, J., Taccioli, G., and Chen, J. (1992) V-D-J recombination. Immunol. Today 13, 306–314.PubMedCrossRefGoogle Scholar
  4. 4.
    Melchers, F., Karasuyama, H., Haasner, D., Bauer, S., Kudo, A., Sakaguchi, N., Jameson, B., and Rolink, A. (1993) The surrogate light chain in B-cell development. Immunol. Today 14, 60–68.PubMedCrossRefGoogle Scholar
  5. 5.
    Rolink, A., Grawunder, U., Winkler, T. H., Karasuyama, H., and Melchers, F. (1994) IL-2 receptor a chain (CD25, TAC) expression defines a crucial stage in pre-B cell development. Int. Immunol. 6, 1257–1264.Google Scholar
  6. 6.
    Borst, J., Jacobs, H., and Brouns, G. (1996) Composition and function of T cell receptor and B cell receptor complexes on precursor lymphocytes. Curr. Opin. Immunol. 8, 181–190.PubMedCrossRefGoogle Scholar
  7. 7.
    Berek, C. and Ziegner, M. (1993) The maturation of the immune response. Immunol. Today 14, 400–404.PubMedCrossRefGoogle Scholar
  8. 8.
    Hagman, J. and Grosschedl, R. (1994) Regulation of gene expression at early stages of B cell differentiation. Curr. Opin. Immunol. 6, 222–230.PubMedCrossRefGoogle Scholar
  9. 9.
    Singh, H. (1996) Gene targeting reveals a hierarchy of transcription factors regulating specification of lymphoid cell fates. Curr. Opin. Immunol. 8, 160–165.PubMedCrossRefGoogle Scholar
  10. 10.
    Fitzsimmons, D. and Hagman, J. (1996) Regulation of gene expression at early stages of B cell and T cell differentiation. Curr. Opin. Immunol. 8, 166–174.PubMedCrossRefGoogle Scholar
  11. 11.
    Georgopoulos, K., Moore, D., and Derfler, B. (1992) Ikaros, an early lymphoid specific transcription factor and a putative mediator for T cell commitment. Science 258, 808–812.Google Scholar
  12. 12.
    Hahm, K., Ernst, P., Lo, K., Kim, G. S., Turck, C., and Smale, S. T. (1994) The lymphoid transcription factor LyF-1 is encoded by specific, alternatively spliced mRNAs derived from the Ikaros gene. Mol. Cell Biol. 14, 7111–7123.Google Scholar
  13. 13.
    Georgopoulos, K., Bigby, M., Wang, J., Molnar, A., Wu, P., Winandy, S., and Sharpe, A. (1994) The IKAROS gene is required for the development of all lymphoid lineages. Cell 79, 143–156.PubMedCrossRefGoogle Scholar
  14. 14.
    Klemsz, M. J., McKercher,S. R., Celada, A., Van Beveren, C., and Maki, R. A. (1990) The macrophage and B cell-specific transcription factor PU. 1 is related to the ets oncogene. Ce1161, 113–124.Google Scholar
  15. 15.
    Moreau-Gachelin, F. Spi-1/Pu.1 an oncogene of the ets family. (1994) Biochim. Biophys. Acta 1198, 149–163.PubMedGoogle Scholar
  16. 16.
    Scott, E., Simon, M., Anastasi, J., and Singh, H. (1994) Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science 265, 1573–1577.PubMedCrossRefGoogle Scholar
  17. 17.
    Hagman, J., Belanger, C., Travis, A., Turck, C., and Grosschedl, R. (1993) Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression. Genes Dell. 7, 760–773.CrossRefGoogle Scholar
  18. 18.
    Murre, C., Schonleber Mc-Caw, P., and Baltimore, D. (1989a) A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell 56, 777–783.PubMedCrossRefGoogle Scholar
  19. 19.
    Bain G., Robanus Maandag, E., Izon, D., Amsen, D., Kruisbeek, A., Weintraub, B., Krop, I., Schlissel, M., Feeney, A., van Roon, M., van der Valk, M., to Riele, H., Berns, A., and Murre, C. (1994) E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell 79, 885–892.PubMedCrossRefGoogle Scholar
  20. 20.
    Zhuang, Y., Soriano, P., and Weintraub, H. (1994) The helix-loop-helix gene E2A is required for B cell formation. Cell 79, 875–884.PubMedCrossRefGoogle Scholar
  21. 21.
    Lin, H. and Grosschedl, R. (1995) Failure ofB-cell differentiation in mice lacking the transcription factor EBF. Nature 376, 263–267.PubMedCrossRefGoogle Scholar
  22. 22.
    Busslinger, M. and Urbanek, P. (1995) The role of BSAP (Pax-5) in B cell development. Curr. Opin. Genet. Dey. 5, 595–601.CrossRefGoogle Scholar
  23. 23.
    Urbanek, P., Wang, Z.-Q., Fetka, I., Wagner, E., and Busslinger, M. (1994) Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking PaxS/BSAP. Cell 79, 901–912.PubMedCrossRefGoogle Scholar
  24. 24.
    Nutt, S., Urbanek, P., Rolink, A., and Busslinger, M. (1997) Essential functions of Pax-5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoesis and reduced V- to DJ recombination in the IgH locus. Genes Dey. 11, 476–491.CrossRefGoogle Scholar
  25. 25.
    Hagman, J., Travis, A., and Grosschedl, R. (1991) A novel lineage-specific nuclear factor regulates mb-1 gene transcription at the early stages of B cell differentiation. EMBO J. 10, 3409–3417.PubMedGoogle Scholar
  26. 26.
    Feldhaus, A., Mbangkollo, D., Arvin, K., Klug, C. H. S., and Singh, H. (1992) B1yF, a novel cell-type-and stage-specific regulator of the B-lymphocyte gene mb-1. Mol. Cell Biol. 12, 1126–1133.Google Scholar
  27. 27.
    Kudrycki, K., Stein-Izsak, C., Behn, C., Grillo, M., Akeson, R., and Margolis, F. (1993) Olf-1 binding site: Characterisation of an olfactory neuron specific promoter motif. Mol. Cell. Biol. 13, 3002–3014.PubMedGoogle Scholar
  28. 28.
    Wang, M. and Reed, R. (1993) Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast. Nature 364, 121–126.PubMedCrossRefGoogle Scholar
  29. 29.
    Travis, A., Hagman, J., Hwang, L., and Grosschedl, R. (1993) Purification of early-B-cell factor and characterization of its DNA-binding specificity. Mol. Cell. Biol. 13, 3392–3400.PubMedGoogle Scholar
  30. 30.
    Crozatier, M., Valle, D., Dubois, L., Ibnsouda, S., and Vincent, A. (1996) Collier, a novel regulator of Drosophila head development, is expressed in a single mitotic domain. Curr. Biol. 6, 707–718.Google Scholar
  31. 31.
    Hagman, J., Gutch, M., Lin, H., and Grosschedl, R. (1995) EBF contains a novel zinc coordination motif and multiple dimerization and transcriptional activation domains. EMBO J. 14, 2907–2916.PubMedGoogle Scholar
  32. 32.
    Sigvardsson, M., Âkerblad, P., and Leanderson, T. (1996) Early B cell Factor interacts with a subset of x promoters. J. Immunol. 156, 3788–3796.PubMedGoogle Scholar
  33. 33.
    Sigvardsson, M., O’Riordan, M., and Grosschedl, R. (1997) EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. Immunity, 7, 25–36.PubMedCrossRefGoogle Scholar
  34. 34.
    Molnar, A. and Georgopoulos, K. (1994) The IKAROS gene encodes a family of functionally diverse zinc finger DNA-binding proteins. Mol. Cell. Biol. 14, 8292–8303.PubMedGoogle Scholar
  35. 35.
    Morgan, B., Sun, L., Avitahl, N., Andrikopolous, K., Ikeda, T., Gonzales, E., Wu, P., Neben, S., and Georgopolous, K. (1997) Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation. EMBO J. 16, 2004–2013.Google Scholar
  36. 36.
    Sun, L., Aiping, L., and Georgopoulos, K. (1996) Zinc finger-mediated protein interactions modulate Ikaros activity, a molecular control of lymphocyte development. EMBO J. 15, 5358–5369.PubMedGoogle Scholar
  37. 37.
    Travis, A., Hagman, J., and Grosschedl, R. (1991) Heterogeneously initiated transcription from the Pre-B- and B-cell-specific mb-1 promoter: Analysis of the requirement for upstream factor-binding sites and initiation site sequences. Mol. Cell Biol. 11, 5756–5766.PubMedGoogle Scholar
  38. 38.
    Fitzsimmons, D., Hodsdon, W., Wheat, W., Maira, S.-M., Wasylyk, B., and Hagman, J. (1996) Pax-5 (BSAP) recruits Ets proto-oncogene family proteins to form functional ternary complexes on a B-cell-specific promoter. Genes Dey. 10, 2198–2211.CrossRefGoogle Scholar
  39. 39.
    Kozmik, Z., Wang, S., Dorfier, P., Adams, B., and Busslinger, M. (1992) The promoter of the CD 19 gene is a target for the B cell specific transcription factor BSAP. Mol. Cell. Biol. 12, 2662–2672.PubMedGoogle Scholar
  40. 40.
    Zwollo, P. and Desiderio, S. (1994) Specific recognition of the blk promoter by the B lymphoid transcription factor B-cell-specific activator protein. J. Biol. Chem. 269, 15310–15317.PubMedGoogle Scholar
  41. 41.
    Rinkenberger, J., Wallin, J., Johnson, K., and Koshland, M. (1996) An interleukin-2 signal relieves the BSAP (PaxS)-mediated repression of the immunoglobulin J chain gene. Immunity 5, 377–386.CrossRefGoogle Scholar
  42. 42.
    Singh, M. and Birshtein, B. K. (1993) NF-HB (BSAP) is a repressor of the murine immunoglobulin heavy-chain 3’a enhancer at early stages of B-cell differentiation. Mol. Cell Biol. 13, 3611–3622.PubMedGoogle Scholar
  43. 43.
    Neurath, M., Stuber, E., and Wakatsuki, Y. (1994) The murine Ig 3’ a enhancer is a target site with repressor function for the B cell lineage-specific transcription factor BSAP. J. Immunol. 153, 730–742.PubMedGoogle Scholar
  44. 44.
    Neurath, M. F., Max, E. E., and Strober, W. (1995) PaxS (BSAP) regulates the murine immunoglobulin 3’a enhancer by suppressing binding of NF-aP, a protein that controls heavy chain transcription. Proc. Natl. Acad. Sci. USA 92, 5336–5340.PubMedCrossRefGoogle Scholar
  45. 45.
    Henthorn, P., Kiledjian, M., and Kadesch, T. (1990) Two distinct transcription factors that bind the immunoglobulin enhancer 1..1E5/KE2 motif. Science 247, 467–470.PubMedCrossRefGoogle Scholar
  46. 46.
    Nelson, C., Shen, L.-P., Meister, A., Fodor, E., and Rutter, W. J. (1990) Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs. Genes Del/. 4, 1035–1043.Google Scholar
  47. 47.
    Hu, J.-S., Olson, E. N., and Kingston, R. E. (1992) HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenia regulatory factors. Mol. Cell. Biol. 12, 1031–1042.PubMedGoogle Scholar
  48. 48.
    Murre, C., Bain, G., van Dijk, M., Engel, I., Furnari, B., Massari, M., Matthews, J., Quong, M., Rivera, R., and Stuiver, M. (1994) Structure and function of helix-loop-helix proteins. Bioch. et Bioph. Acta 1218, 129–135.Google Scholar
  49. 49.
    Löscher, B. and Eisenman, R. (1990) New light on myc and myb. Part 1 myc. Genes Dey. 4, 2025–2035.CrossRefGoogle Scholar
  50. 50.
    Benezra, R., Davis, R., Lockshon, D., Turner, D., and Weintraub, H. (1990) The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 61, 49–59.PubMedCrossRefGoogle Scholar
  51. 51.
    Wilson, R., Kiledjian, M., Shen, C.-P., Benezra, R., Zwollo, P., Dymecki, S., Desiderio, S., and Kadesch, T. (1991) Repression of immunoglobulin enhancers by the helix-loop-helix protein Id: implications for B-lymphoid-cell development. Mol. Cell. Biol. 11, 6185–6191.Google Scholar
  52. 52.
    Bain G., Gruenwald, S., and Murre, C. (1993) E2A and E2–2 are subunits of B-cell-specific E2-box DNA-binding proteins. Mol. Cell. Biol. 13, 3522–3529.PubMedGoogle Scholar
  53. 53.
    Jacobs, Y., Xin, X.-Q., Dorshkind, K., and Nelson, C. (1994) Pan/E2A expression precedes immunoglobulin heavy-chain expression during B lymphopoiesis in nontransformed cells, and Pan/E2A proteins are not detected in myeloid cells. Mol. Cell Biol. 14, 4087–4096.PubMedGoogle Scholar
  54. 54.
    Murre, C., Schonleber Mc-Caw, P., Vaessin, H., Caudy, M., Jan, L., Jan, Y., Cabrera, C., Buskin, J., Hauschka, S., Lassar, A., Weintraub, H., and Baltimore, D. (1989b) Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58, 537–544.PubMedCrossRefGoogle Scholar
  55. 55.
    Brennan, T. and Olson, E. (1990) Myogenin resides in the nucleus and acquires high affinity for a conserved enhancer element upon heterodimerization. Genes Del). 4 582–595.Google Scholar
  56. 56.
    Lassar, A., Davis, R., Wright, W., Kadesch, W. T., Murre, C., Vovonova, A., Baltimore, D., and Weintraub, H. (1991) Functional activity of myogenic bHLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell 66, 305–315.Google Scholar
  57. 57.
    Shen, C.-P. and Kadesch, T. (1995) B cell specififc DNA binding by an E47 homodimer. Mol. Cell. Biol. 15, 4518–4524.PubMedGoogle Scholar
  58. 58.
    Benezra, R. (1995) An intermolecular disulfide bond stabilizes E2A homodimers and is required for DNA binding at physiological temperatures. Cell 79, 1057–1067.CrossRefGoogle Scholar
  59. 59.
    Sloan, S., Shen, C.-P., McGarrick-Walmsley, R., and Kadesch, T. (1996) Phosphorylation of E47 as a potential determinant of B cell specific activity. Mol. Cell. Biol. 16, 6900–6908.PubMedGoogle Scholar
  60. 60.
    Murre, C., Voronova, A., and Baltimore, D. (1991) B-cell-and myocyte-specific E2-boxbinding factors contain E12/E47-like subunits. Mol. Cell. Biol. 11, 1156–1160.PubMedGoogle Scholar
  61. 61.
    Saisanit, S. and Sun, X.-H. (1995) A novel enhancer, the pro-B enhancer, regulates Idl gene expression in progenitor B cells. Mol. Cell Biol. 15, 1513–1521.PubMedGoogle Scholar
  62. 62.
    Ephrussi, A., Church, G., Tonegawa, S., and Gilbert, W. (1985) B-lineage-specific interactions of a immunoglobulin enhancer with cellular factors in vivo. Science 227, 134–140.PubMedCrossRefGoogle Scholar
  63. 63.
    Alex, R., Sozeri, O., Meyer, S., and Dildrop, R. (1992) Determination of the DNA sequence recognized by the bHLH domain of the N-myc protein. Nucleic Acids Res. 20, 2257–2263.PubMedCrossRefGoogle Scholar
  64. 64.
    Blackwell, T., Huang, J., Ma, A., Kretzner, L., Alt, F., Eisenman, R., and Weintraub, H. (1993) Binding of myc proteins to canonical and noncanonical DNA sequences. Mol. Cell. Biol. 13, 5216–5224.PubMedGoogle Scholar
  65. 65.
    Davis, R., Cheng, P., Lassar, A., and Weintraub, H. (1990) The MyoD DNA binding domain contains a recognition code for muscle specific gene activation. Cell 60, 733–746.PubMedCrossRefGoogle Scholar
  66. 66.
    Ellenberger, T., Fass, D., Arnaud, M., and Harrison, S. (1994) Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer. Genes Dey. 8, 970–980.CrossRefGoogle Scholar
  67. 67.
    Quong, M., Massari, M., Zwart, R., and Murre, C. (1993) A new transcriptional activation motif restricted to a class of Helix-loop-helix proteins is functionally conserved in both yeast and mammalian cells. Mol. Cell. Biol. 13, 792–800.PubMedGoogle Scholar
  68. 68.
    Olsen, E. (1990) MyoD family: a paradigm for development? Genes Del/. 4, 1454–1461.CrossRefGoogle Scholar
  69. 69.
    Wright, W. (1992) Muscle basic helix-loop-helix proteins and the regulation of myogenisis. Curr. Opin. Genet. Del/. 2, 243–248.CrossRefGoogle Scholar
  70. 70.
    Peverali, F., Ramqvist, T., Saffrich, R., Pepperkok, R., Barone, M., and Philipson, L. (1994) Regulation of G1 progression by E2A and Id helix-loop-helix proteins. EMBO J. 13, 4291–4301.PubMedGoogle Scholar
  71. 71.
    Sun, X.-H. (1994) Constitutive expression of the Idl gene impairs mouse B cell development. Cell 79, 893–900.PubMedCrossRefGoogle Scholar
  72. 72.
    Ernst, P. and Smale, S. (1995) Combinatorial regulation of transcription II: the immunoglobulin p heavy chain gene. Immunity 2, 427–438.PubMedCrossRefGoogle Scholar
  73. 73.
    Adams, J., Harris, A., Pinkert, C., Corcoran, L., Alexander, W., Cory, S., Palmiter, R., and Brinster, R. (1985) The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 318, 533–538.PubMedCrossRefGoogle Scholar
  74. 74.
    Stanton, L., Watt, R., and Marcu, K. (1983) Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasma-cytomas. Nature 303, 401–406.PubMedCrossRefGoogle Scholar
  75. 75.
    Schlissel, M., Voronova, A., and Baltimore, D. (1991) Helix-loop-helix transcription factor E47 activates germ-line immunoglobulin heavy-chain gene transcription and rearrangement in a pre-T-cell line. Genes Dev. 5, 1367–1376.PubMedCrossRefGoogle Scholar
  76. 76.
    Choi, J., Shen, C.-P., Radomska, H., Eckhardt, L., and Kadesch, T. (1996) E47 activates the Igheavy chain and TdT loci in non-B cells. EMBO J. 15, 5014–5021.PubMedGoogle Scholar
  77. 77.
    Lennon, G. and Perry, R. (1985) C p-containing transcripts initiate heterogeneously within the IgH enhancer region and contain a novel 5’-nontranslatable exon. Nature 318, 475–478.PubMedCrossRefGoogle Scholar
  78. 78.
    Su, L. and Kadesch, T. (1990) The immunoglobulin heavy chain enhancer functions as the promoter for Ip sterile transcription. Mol. Cell. Biol. 10, 2619–2624.PubMedGoogle Scholar
  79. 79.
    Alt, F., Blackwell, T., and Yancopoulos, G. (1987) Development of the primary antibody repertoire. Science 238, 1079–1087.PubMedCrossRefGoogle Scholar
  80. 80.
    Lenardo, M., Pierce, J., and Baltimore, D. (1987) Protein binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science 236, 1573–1577.PubMedCrossRefGoogle Scholar
  81. 81.
    Park, K. and Atchison, M. L. (1991) Isolation of a candidate repressor/activator, NF-El (YY1, 6), that binds to the immunoglobulin x 3’ enhancer and the immunoglobulin heavy-chain p El site. Proc. Natl. Acad. Sci. USA 88, 9804–9808.PubMedCrossRefGoogle Scholar
  82. 82.
    Nelsen, B., Tian, G., Erman, B., Gregoire, J., Maki, R., Graves, B., and Sen, R. (1993) Regulation of lymphoid specific Immunoglobulin m heavy chain gene enhancer by ets-domain proteins. Science 261, 82–86.PubMedCrossRefGoogle Scholar
  83. 83.
    Rivera, R. S., Stuiver, M. H., Steenbergen, R., and Murre, C. (1993) Ets proteins: New factors that regulate inununoglobulin heavy-chain gene expression. Mol. Cell Biol. 13, 7163–7169.Google Scholar
  84. 84.
    Erman, B. and Sen, R. (1996) Context-dependent transactivation domains activate the immunoglobulin-.t heavy-chain gene enhancer. EMBO J. 15, 4665–4675.PubMedGoogle Scholar
  85. 85.
    Kadesch, T. (1992) Helix-loop-helix proteins in the regulation of immunoglobulin gene transcription. Immunol. Today 13, 31–36.PubMedCrossRefGoogle Scholar
  86. 86.
    Sun, X.-H., Copeland, N. A., Jenkins, N. A., and Baltimore, D. (1991) Id proteins Id l and Id2 selectively inhibit DNA binding by one class of helix-loop-helix proteins. Mol. Cell Biol. 11, 5603–5611.PubMedGoogle Scholar
  87. 87.
    Ruezinsky, D., Beckmann, H., and Kadesch, T. (1991) Modulation of the IgH enhancer’s cell type specificity through a genetic switch. Genes Dey. 5, 29–37.CrossRefGoogle Scholar
  88. 88.
    Williams, T. W., Moolten, D., Burlien, J., Romano, J., Bhaerman, R., Godillot, A., Mellon, M., Rauscher, F. J., III, and Kant, J. A. (1991) Identification of a zinc finger protein that inhibits IL-2 gene expression. Science 254, 1791–1794.PubMedCrossRefGoogle Scholar
  89. 89.
    Genetta, T., Ruezinsky, D., and Kadesch, T. (1994) Displacement of an E-box-binding repressor by basic helix-loop-helix proteins: implications for B-cell specificity of the immunoglobulin heavy-chain enhancer. Mol. Cell. Biol. 14, 6153–6163.PubMedCrossRefGoogle Scholar
  90. 90.
    Bain G., Robanus Maandag, E., te Riele, H., Feeney, A., Sheeny, A., Schlissel, M., Shinton, A., Hardy, R., and Murre, C. (1997) Both E12 and E47 allow commitment to the B cell lineage. Immunity 6, 145–154.PubMedCrossRefGoogle Scholar
  91. 91.
    Zhuang, Y., Cheng, P., and 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.PubMedGoogle Scholar
  92. 92.
    Kudo, A., Sakaguchi, N., and Melchers, F. (1987) Organization of the murine Ig-related X,5 gene transcribed selectively in pre-B lymphocytes. EMBO J. 6, 103–107.PubMedGoogle Scholar
  93. 93.
    Yang, J., Glozak, M., and Blomberg, B. (1995) Identification and localization of a developmental stage-specific promoter activity from the murine X5 gene. J. Immunol. 155, 2498–2514.PubMedGoogle Scholar

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© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Mikael Sigvardsson
  • Rudolf Grosschedl

There are no affiliations available

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