Transcriptional regulation in early B cell development

Current Opinion in Immunology

Volumn 19, Issue 2, 2007, Pages 129-136

  Fuxa, Martin ^a   Skok, Jane A ^a,b  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CIS ACTING ELEMENT; FLT3 LIGAND; IMMUNOGLOBULIN; LYMPHOCYTE ANTIGEN RECEPTOR; RECOMBINASE; TRANSCRIPTION FACTOR E47; TRANSCRIPTION FACTOR FOXP1; TRANSCRIPTION FACTOR PAX5; UNCLASSIFIED DRUG;

ALLELE; B LYMPHOCYTE; CELL LINEAGE; ENZYME REPRESSION; GENE ACTIVATION; GENE LOCUS; GENE REARRANGEMENT; GENETIC RECOMBINATION; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; SYSTEMATIC REVIEW; TRANSCRIPTION REGULATION;

ALLELES; ANIMALS; B-CELL-SPECIFIC ACTIVATOR PROTEIN; B-LYMPHOCYTES; CELL LINEAGE; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENE REARRANGEMENT, B-LYMPHOCYTE; LYMPHOPOIESIS; MICE; REPRESSOR PROTEINS; TCF TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 33847632440     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coi.2007.02.002     Document Type: Review

References (45)

1. Akashi K., Traver D., Miyamoto T., and Weissman I.L. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404 (2000) 193-197
2. + lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell 121 (2005) 295-306
3. Busslinger M. Transcriptional control of early B cell development. Annu Rev Immunol 22 (2004) 55-79
4. W/W mutants reveal pivotal role for c-kit in the maintenance of lymphopoiesis. Immunity 17 (2002) 277-288
5. Vosshenrich C.A., Cumano A., Muller W., Di Santo J.P., and Vieira P. Thymic stromal-derived lymphopoietin distinguishes fetal from adult B cell development. Nat Immunol 4 (2003) 773-779
6. Medina K.L., and Singh H. Genetic networks that regulate B lymphopoiesis. Curr Opin Hematol 12 (2005) 203-209
7. Dakic A., Metcalf D., Di Rago L., Mifsud S., Wu L., and Nutt S.L. PU.1 regulates the commitment of adult hematopoietic progenitors and restricts granulopoiesis. J Exp Med 201 (2005) 1487-1502
8. Allman D., and Miller J.P. Common lymphoid progenitors, early B-lineage precursors, and IL-7: characterizing the trophic and instructive signals underlying early B cell development. Immunol Res 27 (2003) 131-140
9. Liu P., Keller J.R., Ortiz M., Tessarollo L., Rachel R.A., Nakamura T., Jenkins N.A., and Copeland N.G. Bcl11a is essential for normal lymphoid development. Nat Immunol 4 (2003) 525-532
10. Nutt S.L., Urbanek P., Rolink A., and Busslinger M. 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 (1997) 476-491
11. Nutt S.L., Heavey B., Rolink A.G., and Busslinger M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 401 (1999) 556-562
12. Nutt S.L., Morrison A.M., Dorfler P., Rolink A., and Busslinger M. Identification of BSAP (Pax-5) target genes in early B-cell development by loss- and gain-of-function experiments. EMBO J 17 (1998) 2319-2333
13. Horcher M., Souabni A., and Busslinger M. Pax5/BSAP maintains the identity of B cells in late B lymphopoiesis. Immunity 14 (2001) 779-790
14. Schebesta M., Pfeffer P.L., and Busslinger M. Control of pre-BCR signaling by Pax5-dependent activation of the BLNK gene. Immunity 17 (2002) 473-485
15. Souabni A., Cobaleda C., Schebesta M., and Busslinger M. Pax5 promotes B lymphopoiesis and blocks T cell development by repressing Notch1. Immunity 17 (2002) 781-793
16. -/- pro-B cells and common lymphoid progenitors display lymphoid and myeloid promiscuity of gene expression. Conditional deletion of Pax5 in committed pro-B cells and mature B cells demonstrates that Pax5 activity is continuously required for the repression of these lineage-inappropriate genes. Pax5-repressed genes are also reactivated in plasma cells, indicating that the physiological loss of Pax5 during terminal differentiation contributes to the plasma cell transcription program.
17. Holmes M.L., Carotta S., Corcoran L.M., and Nutt S.L. Repression of Flt3 by Pax5 is crucial for B-cell lineage commitment. Genes Dev 20 (2006) 933-938. The role of Pax5 in lineage commitment is extended by the finding that Pax5 represses a crucial growth factor receptor, Flt3, which is required for efficient formation of early lymphoid progenitors. Pax5-deficient pro-B cells express abundant Flt3 that is rapidly silenced upon the introduction of Pax5, which binds to the Flt3 promoter in vivo. Enforced expression of Flt3 in wild-type progenitors significantly impairs B-cell development and indicates that the repression of Flt3 by Pax5 is essential for normal B-lymphopoiesis.
18. Hesslein D.G., and Schatz D.G. Factors and forces controlling V(D)J recombination. Adv Immunol 78 (2001) 169-232
19. Bassing C.H., Swat W., and Alt F.W. The mechanism and regulation of chromosomal V(D)J recombination. Cell 109 (2002) S45-S55
20. Schlissel M.S. Regulating antigen-receptor gene assembly. Nat Rev Immunol 3 (2003) 890-899
21. Yancopoulos G.D., and Alt F.W. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell 40 (1985) 271-281
22. Kosak S.T., Skok J.A., Medina K.L., Riblet R., Le Beau M.M., Fisher A.G., and Singh H. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 296 (2002) 158-162
23. Sato H., Saito-Ohara F., Inazawa J., and Kudo A. Pax-5 is essential for κ sterile transcription during Ig κ chain gene rearrangement. J Immunol 172 (2004) 4858-4865
24. Fuxa M., Skok J., Souabni A., Salvagiotto G., Roldan E., and Busslinger M. Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. Genes Dev 18 (2004) 411-422
25. H rearranged IgH allele, and centromeric recruitment, which repositions the non-functional allele within a repressive subcompartment of the nucleus during IgL rearrangement. Thus, both decontraction and centromeric recruitment are important for establishing allelic exclusion.
26. Taddei A., and Gasser S.M. Multiple pathways for telomere tethering: functional implications of subnuclear position for heterochromatin formation. Biochim Biophys Acta 1677 (2004) 120-128
27. Schmid M., Arib G., Laemmli C., Nishikawa J., Durussel T., and Laemmli U.K. Nup-PI: the nucleopore-promoter interaction of genes in yeast. Mol Cell 21 (2006) 379-391
28. Yang Q., Riblet R., and Schildkraut C.L. Sites that direct nuclear compartmentalization are near the 5′ end of the mouse immunoglobulin heavy-chain locus. Mol Cell Biol 25 (2005) 6021-6030
29. Romanow W.J., Langerak A.W., Goebel P., Wolvers-Tettero I.L., van Dongen J.J., Feeney A.J., and Murre C. E2A and EBF act in synergy with the V(D)J recombinase to generate a diverse immunoglobulin repertoire in nonlymphoid cells. Mol Cell 5 (2000) 343-353
30. Goebel P., Janney N., Valenzuela J.R., Romanow W.J., Murre C., and Feeney A.J. 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 (2001) 645-656
31. Bolland D.J., Wood A.L., Johnston C.M., Bunting S.F., Morgan G., Chakalova L., Fraser P.J., and Corcoran A.E. Antisense intergenic transcription in V(D)J recombination. Nat Immunol 5 (2004) 630-637
32. McBlane F., and Boyes J. Stimulation of V(D)J recombination by histone acetylation. Curr Biol 10 (2000) 483-486
33. Chowdhury D., and Sen R. Stepwise activation of the immunoglobulin μ heavy chain gene locus. EMBO J 20 (2001) 6394-6403
34. Maes J., O'Neill L.P., Cavelier P., Turner B.M., Rougeon F., and Goodhardt M. Chromatin remodeling at the Ig loci prior to V(D)J recombination. J Immunol 167 (2001) 866-874
35. Hsu L.Y., Lauring J., Liang H.E., Greenbaum S., Cado D., Zhuang Y., and Schlissel M.S. A conserved transcriptional enhancer regulates RAG gene expression in developing B cells. Immunity 19 (2003) 105-117
36. H rearrangements and a profound arrest before the pro-B cell stage. Other downstream lymphoid progeny of CLPs are, however, still intact in these mice, albeit at reduced numbers. Although recombinase activity is inhibited in early B lineage precursors in E47-deficient animals, loss of either E47 or its cis-acting target Erag has little effect on recombinase activity in thymic T lineage precursors. This report defines a role for E47 in lineage progression at the CLP stage and in regulating B cell specific recombinase activity.
37. +/- compound heterozygous mice. This report identifies Foxp1 as an essential participant in the transcriptional regulatory network of B lymphopoiesis.
38. Jung D., Giallourakis C., Mostoslavsky R., and Alt F.W. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol 24 (2006) 541-570
39. Chowdhury D., and Sen R. Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements. Immunity 18 (2003) 229-241
40. Goldmit M., Ji Y., Skok J., Roldan E., Jung S., Cedar H., and Bergman Y. Epigenetic ontogeny of the Igκ locus during B cell development. Nat Immunol 6 (2005) 198-203. This study analyzes the epigenetic changes that occur at the Igκ locus during B-cell development. The authors report that, in pre-B cells, one allele is preferentially packaged into active chromatin whereas the other allele is repositioned at centromereric heterochromatin and is associated with HP1 and Ikaros.
41. Liu Z., Widlak P., Zou Y., Xiao F., Oh M., Li S., Chang M.Y., Shay J.W., and Garrard W.T. A recombination silencer that specifies heterochromatin positioning and Ikaros association in the immunoglobulin κ locus. Immunity 24 (2006) 405-415. Using yeast artificial chromosome-based single-copy isotransgenic mice, these authors identified a cis-acting element residing in the V-J intervening sequence. This element, termed Sis, negatively regulates rearrangement in this locus and appears necessary for targeting germline Igκ transgenes to centromeric heterochromatin in pre-B and B cells. Sis is furthermore shown to associate with Ikaros - a repressor protein that also colocalizes with centromeric heterochromatin. The data suggest that Sis participates in the monoallelic silencing aspect of allelic exclusion regulation through targeting to centromeric heterochromatin domains.
42. Liang H.E., Hsu L.Y., Cado D., and Schlissel M.S. Variegated transcriptional activation of the immunoglobulin κ locus in pre-B cells contributes to the allelic exclusion of light-chain expression. Cell 118 (2004) 19-29
43. Inlay M.A., Lin T., Gao H.H., and Xu Y. Critical roles of the immunoglobulin intronic enhancers in maintaining the sequential rearrangement of IgH and Igκ loci. J Exp Med 203 (2006) 1721-1732. To identify cis-acting elements that regulate ordered rearrangement, the authors of this study replaced the endogenous matrix attachment region/Igκ intronic enhancer (MiEκ) with its heavy chain counterpart (Eμ). Replacement substantially increases accessibility of both Vκ and Jκ segments to the recombinase enzymes in pro-B cells and induces Igκ rearrangement in these cells. Replacement loci, however, do not support Igκ rearrangement in pre-B cells. This suggests an important role for Eμ and MiEκ in stage-specific ordered rearrangement.
44. Maier H., Ostraat R., Gao H., Fields S., Shinton S.A., Medina K.L., Ikawa T., Murre C., Singh H., Hardy R.R., et al. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nat Immunol 5 (2004) 1069-1077
45. Roessler S, Györy I, Imhof S, Spivakov M, Williams RR, Busslinger M, Fisher AG, Grosschedl R: Distinct promoters mediate the regulation of Ebf1 gene expression by IL-7 and Pax5. Mol Cell Biol 2006, in press.