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PMID: 20452952 Published · ppublish English Journal Article Review

Roles of the NF-kappaB pathway in lymphocyte development and function.

Cold Spring Harbor perspectives in biology ·Vol. 2 ·No. 5 ·2010-05-00 ·Pages a000182

Gerondakis S, Siebenlist U

Abstract

This article focuses on the functions of NF-kappaB that vitally impact lymphocytes and thus adaptive immunity. NF-kappaB has long been known to be essential for many of the responses of mature lymphocytes to invading pathogens. In addition, NF-kappaB has important functions in shaping the immune system so it is able to generate adaptive responses to pathogens. In both contexts, NF-kappaB executes critical cell-autonomous functions within lymphocytes as well as within supportive cells, such as antigen-presenting cells or epithelial cells. It is these aspects of NF-kappaB's physiologic impact that we address in this article.

MeSH Terms
Animals Humans Lymphocytes/cytology NF-kappa B/physiology
Chemicals
NF-kappa B
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gerondakis Steve
The Burnet Institute, 85 Commercial Rd, Prahran, Victoria 3004, Australia. gerondakis@burnet.edu.au
Siebenlist Ulrich
References (230)
230 references, click to expand
  1. Deciphering the pathway from the TCR to NF-kappaB.
    Cell Death Differ. 2006 May;13(5):826-33 PMID: 16439988
  2. Development of immunoglobulin lambda-chain-positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappaB signals.
    Nat Immunol. 2009 Jun;10(6):647-54 PMID: 19412180
  3. B cell receptor basal signaling regulates antigen-induced Ig light chain rearrangements.
    J Immunol. 2008 Apr 1;180(7):4728-41 PMID: 18354197
  4. PKC theta mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia.
    Oncogene. 2005 Feb 3;24(6):992-1000 PMID: 15592506
  5. CARMA1, BCL-10 and MALT1 in lymphocyte development and activation.
    Nat Rev Immunol. 2004 May;4(5):348-59 PMID: 15122200
  6. Abnormal organogenesis of Peyer's patches in mice deficient for NF-kappaB1, NF-kappaB2, and Bcl-3.
    Gastroenterology. 2002 Jun;122(7):1853-68 PMID: 12055593
  7. Essential role of nuclear factor (NF)-kappaB-inducing kinase and inhibitor of kappaB (IkappaB) kinase alpha in NF-kappaB activation through lymphotoxin beta receptor, but not through tumor necrosis factor receptor I.
    J Exp Med. 2001 Mar 5;193(5):631-6 PMID: 11238593
  8. Antigen-specific memory B cell development.
    Annu Rev Immunol. 2005;23:487-513 PMID: 15771579
  9. The mitogen-induced increase in T cell size involves PKC and NFAT activation of Rel/NF-kappaB-dependent c-myc expression.
    Immunity. 2004 Jul;21(1):19-30 PMID: 15345217
  10. The many roles of FAS receptor signaling in the immune system.
    Immunity. 2009 Feb 20;30(2):180-92 PMID: 19239902
  11. Cell-autonomous role for NF-kappa B in immature bone marrow B cells.
    J Immunol. 2009 Mar 15;182(6):3406-13 PMID: 19265118
  12. Development of secondary lymphoid organs.
    Annu Rev Immunol. 2008;26:627-50 PMID: 18370924
  13. How the Dorsal gradient works: insights from postgenome technologies.
    Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20072-6 PMID: 19104040
  14. Differential requirement for CARMA1 in agonist-selected T-cell development.
    Eur J Immunol. 2009 Jan;39(1):78-84 PMID: 19130560
  15. PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes.
    Nature. 2000 Mar 23;404(6776):402-7 PMID: 10746729
  16. Developmental stage-dependent collaboration between the TNF receptor-associated factor 6 and lymphotoxin pathways for B cell follicle organization in secondary lymphoid organs.
    J Immunol. 2007 Nov 15;179(10):6799-807 PMID: 17982070
  17. Histone dynamics on the interleukin-2 gene in response to T-cell activation.
    Mol Cell Biol. 2005 Apr;25(8):3209-19 PMID: 15798206
  18. Activation of NF-kappaB1 by OX40 contributes to antigen-driven T cell expansion and survival.
    J Immunol. 2008 Jun 1;180(11):7240-8 PMID: 18490723
  19. Aire.
    Annu Rev Immunol. 2009;27:287-312 PMID: 19302042
  20. Tonic B cell antigen receptor signals supply an NF-kappaB substrate for prosurvival BLyS signaling.
    Nat Immunol. 2008 Dec;9(12):1379-87 PMID: 18978795
  21. A critical role of TAK1 in B-cell receptor-mediated nuclear factor kappaB activation.
    Blood. 2009 May 7;113(19):4566-74 PMID: 19196865
  22. Mice deficient in nuclear factor (NF)-kappa B/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture.
    J Exp Med. 1998 Jan 19;187(2):147-59 PMID: 9432973
  23. The who, how and where of antigen presentation to B cells.
    Nat Rev Immunol. 2009 Jan;9(1):15-27 PMID: 19079135
  24. Important roles for E protein binding sites within the immunoglobulin kappa chain intronic enhancer in activating Vkappa Jkappa rearrangement.
    J Exp Med. 2004 Nov 1;200(9):1205-11 PMID: 15504821
  25. Nuclear factor kappa B is required for the development of marginal zone B lymphocytes.
    J Exp Med. 2000 Oct 16;192(8):1175-82 PMID: 11034607
  26. Inefficient ZAP-70 phosphorylation and decreased thymic selection in vivo result from inhibition of NF-kappaB/Rel.
    J Immunol. 2001 Nov 15;167(10):5628-35 PMID: 11698434
  27. Loss of protein kinase C theta, Bcl10, or Malt1 selectively impairs proliferation and NF-kappa B activation in the CD4+ T cell subset.
    J Immunol. 2008 Nov 1;181(9):6244-54 PMID: 18941215
  28. Distinct roles of different NF-kappa B subunits in regulating inflammatory and T cell stimulatory gene expression in dendritic cells.
    J Immunol. 2007 Jun 1;178(11):6777-88 PMID: 17513725
  29. The thymic medulla: a unique microenvironment for intercellular self-antigen transfer.
    J Exp Med. 2009 Jul 6;206(7):1505-13 PMID: 19564355
  30. c-Rel-dependent priming of naive T cells by inflammatory cytokines.
    Immunity. 2005 Oct;23(4):445-58 PMID: 16226509
  31. New regulators of NF-kappaB in inflammation.
    Nat Rev Immunol. 2008 Nov;8(11):837-48 PMID: 18927578
  32. NF-kappaB inducible genes BCL-X and cyclin E promote immature B-cell proliferation and survival.
    Cell Immunol. 2004 Nov-Dec;232(1-2):9-20 PMID: 15922711
  33. Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines.
    J Immunol. 2001 Aug 15;167(4):1909-19 PMID: 11489970
  34. BAFF and the plasticity of peripheral B cell tolerance.
    Curr Opin Immunol. 2008 Apr;20(2):158-61 PMID: 18456486
  35. Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function.
    Semin Immunol. 2008 Feb;20(1):14-25 PMID: 18261920
  36. Essential role of IkappaB kinase alpha in thymic organogenesis required for the establishment of self-tolerance.
    J Immunol. 2006 Apr 1;176(7):3995-4002 PMID: 16547234
  37. Receptor editing in lymphocyte development and central tolerance.
    Nat Rev Immunol. 2006 Oct;6(10):728-40 PMID: 16998507
  38. The roles of CARMA1, Bcl10, and MALT1 in antigen receptor signaling.
    Semin Immunol. 2004 Dec;16(6):429-35 PMID: 15541657
  39. The unconventional role of LT alpha beta in T cell differentiation.
    Trends Immunol. 2007 Apr;28(4):169-75 PMID: 17336158
  40. Secondary lymphoid organs: responding to genetic and environmental cues in ontogeny and the immune response.
    J Immunol. 2009 Aug 15;183(4):2205-12 PMID: 19661265
  41. Signatures of the immune response.
    Immunity. 2001 Sep;15(3):375-85 PMID: 11567628
  42. CpG motifs in bacterial DNA and their immune effects.
    Annu Rev Immunol. 2002;20:709-60 PMID: 11861616
  43. A central role for central tolerance.
    Annu Rev Immunol. 2006;24:571-606 PMID: 16551260
  44. Molecular mechanisms that control mouse and human TCR-alphabeta and TCR-gammadelta T cell development.
    Semin Immunopathol. 2008 Dec;30(4):383-98 PMID: 18925397
  45. Mice lacking the transcription factor subunit Rel can clear an influenza infection and have functional anti-viral cytotoxic T cells but do not develop an optimal antibody response.
    Int Immunol. 1999 Sep;11(9):1431-9 PMID: 10464164
  46. Human T-cell leukemia virus type I Tax-protein-mediated activation of NF-kappa B from p100 (NF-kappa B2)-inhibited cytoplasmic reservoirs.
    Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12634-8 PMID: 7809091
  47. NF-kappa B: a family of inducible and differentially expressed enhancer-binding proteins in human T cells.
    Proc Natl Acad Sci U S A. 1990 Dec;87(24):10028-32 PMID: 2263603
  48. NKT cells turn ten.
    Nat Immunol. 2009 Jul;10(7):669-71 PMID: 19536187
  49. B lymphocytes differentially use the Rel and nuclear factor kappaB1 (NF-kappaB1) transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogen-activated cells.
    J Exp Med. 1998 Mar 2;187(5):663-74 PMID: 9480976
  50. The E2F1-3 transcription factors are essential for cellular proliferation.
    Nature. 2001 Nov 22;414(6862):457-62 PMID: 11719808
  51. Proteolysis of NF-kappaB1 p105 is essential for T cell antigen receptor-induced proliferation.
    Nat Immunol. 2009 Jan;10(1):38-47 PMID: 19060899
  52. Potential role of CARMA1 in CD40-induced splenic B cell proliferation and marginal zone B cell maturation.
    Eur J Immunol. 2006 Nov;36(11):3033-43 PMID: 17048267
  53. NF-kappaB transcription factors: critical regulators of hematopoiesis and neuronal survival.
    Cytokine Growth Factor Rev. 2000 Dec;11(4):303-20 PMID: 10959078
  54. Commitment to the regulatory T cell lineage requires CARMA1 in the thymus but not in the periphery.
    PLoS Biol. 2009 Mar 3;7(3):e51 PMID: 19260764
  55. Control of lymphocyte development by nuclear factor-kappaB.
    Nat Rev Immunol. 2005 Jun;5(6):435-45 PMID: 15905862
  56. Distinct roles for the NF-kappaB1 and c-Rel transcription factors in the differentiation and survival of plasmacytoid and conventional dendritic cells activated by TLR-9 signals.
    Blood. 2005 Nov 15;106(10):3457-64 PMID: 16037393
  57. The lymphotoxin pathway regulates Aire-independent expression of ectopic genes and chemokines in thymic stromal cells.
    J Immunol. 2008 Apr 15;180(8):5384-92 PMID: 18390720
  58. The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell development, survival and function.
    Nat Immunol. 2006 Aug;7(8):851-8 PMID: 16799562
  59. Dominant signals leading to inhibitor kappaB protein degradation mediate CD40 ligand rescue of WEHI 231 immature B cells from receptor-mediated apoptosis.
    J Immunol. 1998 May 1;160(9):4398-405 PMID: 9574544
  60. FK506 inhibits antigen receptor-mediated induction of c-rel in B and T lymphoid cells.
    J Exp Med. 1995 Mar 1;181(3):1091-9 PMID: 7532676
  61. Transcriptional regulation of early B cell development.
    Immunol Res. 2008;42(1-3):106-17 PMID: 18818886
  62. Perturbation of the T lymphocyte lineage in transgenic mice expressing a constitutive repressor of nuclear factor (NF)-kappaB.
    J Exp Med. 1997 Jun 2;185(11):1897-907 PMID: 9166419
  63. Essential function for the kinase TAK1 in innate and adaptive immune responses.
    Nat Immunol. 2005 Nov;6(11):1087-95 PMID: 16186825
  64. CCR7 and its ligands: balancing immunity and tolerance.
    Nat Rev Immunol. 2008 May;8(5):362-71 PMID: 18379575
  65. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance.
    Immunity. 2008 Sep 19;29(3):423-37 PMID: 18799149
  66. The survival of antigen-stimulated T cells requires NFkappaB-mediated inhibition of p73 expression.
    Immunity. 2003 Mar;18(3):331-42 PMID: 12648451
  67. Characterization of an interleukin 4 (IL-4) responsive region in the immunoglobulin heavy chain germline epsilon promoter: regulation by NF-IL-4, a C/EBP family member and NF-kappa B/p50.
    J Exp Med. 1995 Jan 1;181(1):181-92 PMID: 7807002
  68. NF-kappaB guides the survival and differentiation of developing lymphocytes.
    Cell Death Differ. 2006 May;13(5):697-701 PMID: 16528380
  69. Mechanism and control of class-switch recombination.
    Trends Immunol. 2002 Jan;23(1):31-9 PMID: 11801452
  70. CD40 ligand-mediated activation of the de novo RelB NF-kappaB synthesis pathway in transformed B cells promotes rescue from apoptosis.
    J Biol Chem. 2007 Jun 15;282(24):17475-85 PMID: 17446175
  71. IRF4 addiction in multiple myeloma.
    Nature. 2008 Jul 10;454(7201):226-31 PMID: 18568025
  72. Role of nuclear IkappaB proteins in the regulation of host immune responses.
    J Infect Chemother. 2008 Aug;14(4):265-9 PMID: 18709529
  73. NIK overexpression amplifies, whereas ablation of its TRAF3-binding domain replaces BAFF:BAFF-R-mediated survival signals in B cells.
    Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10883-8 PMID: 18663224
  74. T cell-intrinsic expression of c-Rel regulates Th1 cell responses essential for resistance to Toxoplasma gondii.
    J Immunol. 2004 Mar 15;172(6):3704-11 PMID: 15004174
  75. Role of NFkappaB signaling in normal and malignant B cell development.
    Adv Exp Med Biol. 2007;596:149-54 PMID: 17338183
  76. Unravelling the complexities of the NF-kappaB signalling pathway using mouse knockout and transgenic models.
    Oncogene. 2006 Oct 30;25(51):6781-99 PMID: 17072328
  77. Evolution of the immunoglobulin heavy chain class switch recombination mechanism.
    Adv Immunol. 2007;94:157-214 PMID: 17560275
  78. TRAF6 is required for generation of the B-1a B cell compartment as well as T cell-dependent and -independent humoral immune responses.
    PLoS One. 2009;4(3):e4736 PMID: 19270748
  79. Diverse Toll-like receptors utilize Tpl2 to activate extracellular signal-regulated kinase (ERK) in hemopoietic cells.
    Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3274-9 PMID: 16484370
  80. NF-kB inhibitor blocks B cell development at two checkpoints.
    Med Immunol. 2004 Mar 29;3(1):1 PMID: 15050028
  81. Regulating B-cell activation and survival in response to TLR signals.
    Immunol Cell Biol. 2007 Aug-Sep;85(6):471-5 PMID: 17637697
  82. c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription.
    J Exp Med. 2001 Oct 15;194(8):1021-32 PMID: 11602633
  83. Gadd45 beta mediates the protective effects of CD40 costimulation against Fas-induced apoptosis.
    Blood. 2003 Nov 1;102(9):3270-9 PMID: 12855571
  84. I kappa B kinase 2/beta deficiency controls expansion of autoreactive T cells and suppresses experimental autoimmune encephalomyelitis.
    J Immunol. 2007 Jul 1;179(1):179-85 PMID: 17579036
  85. Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells.
    J Exp Med. 2001 Dec 17;194(12):1861-74 PMID: 11748286
  86. Nuclear factor (NF)-kappa B2 (p100/p52) is required for normal splenic microarchitecture and B cell-mediated immune responses.
    J Exp Med. 1998 Jan 19;187(2):185-96 PMID: 9432976
  87. NF-kappaB and the immune response.
    Oncogene. 2006 Oct 30;25(51):6758-80 PMID: 17072327
  88. Dendritic cell development and survival require distinct NF-kappaB subunits.
    Immunity. 2002 Feb;16(2):257-70 PMID: 11869686
  89. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway.
    Science. 2001 Aug 24;293(5534):1495-9 PMID: 11520989
  90. NEMO/IKK gamma-deficient mice model incontinentia pigmenti.
    Mol Cell. 2000 Jun;5(6):981-92 PMID: 10911992
  91. DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes.
    Nature. 2008 Dec 11;456(7223):819-23 PMID: 18849970
  92. The regulation and roles of Rel/NF-kappa B transcription factors during lymphocyte activation.
    Curr Opin Immunol. 1998 Jun;10(3):353-9 PMID: 9638373
  93. The subunit composition of NF-kappa B complexes changes during B-cell development.
    Cell Growth Differ. 1994 Dec;5(12):1321-31 PMID: 7696180
  94. Lymphoid organogenesis in brief.
    Eur J Immunol. 2007 Nov;37 Suppl 1:S46-52 PMID: 17972344
  95. Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation.
    Immunity. 2006 Jun;24(6):729-739 PMID: 16782029
  96. Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function.
    Science. 1997 Jan 24;275(5299):540-3 PMID: 8999800
  97. I kappa B kinase 2 deficiency in T cells leads to defects in priming, B cell help, germinal center reactions, and homeostatic expansion.
    J Immunol. 2004 Aug 1;173(3):1612-9 PMID: 15265889
  98. Antigen receptor signals rescue B cells from TLR tolerance.
    J Immunol. 2009 Sep 1;183(5):2974-83 PMID: 19648281
  99. NF-kappaB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase.
    Mol Cell. 2003 Mar;11(3):685-94 PMID: 12667451
  100. Self/non-self discrimination by human gammadelta T cells: simple solutions for a complex issue?
    Immunol Rev. 2007 Feb;215:123-35 PMID: 17291284
  101. A critical role for NF-kappa B in GATA3 expression and TH2 differentiation in allergic airway inflammation.
    Nat Immunol. 2001 Jan;2(1):45-50 PMID: 11135577
  102. Regulation and function of NF-kappaB transcription factors in the immune system.
    Annu Rev Immunol. 2009;27:693-733 PMID: 19302050
  103. B cell receptor-mediated sustained c-Rel activation facilitates late transitional B cell survival through control of B cell activating factor receptor and NF-kappaB2.
    J Immunol. 2009 Jun 15;182(12):7729-37 PMID: 19494297
  104. The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival.
    J Exp Med. 2005 Feb 21;201(4):603-14 PMID: 15728238
  105. A role for the IkappaB family member Bcl-3 in the control of central immunologic tolerance.
    Immunity. 2007 Sep;27(3):438-52 PMID: 17869136
  106. HS1,2 enhancer regulation of germline epsilon and gamma2b promoters in murine B lymphocytes: evidence for specific promoter-enhancer interactions.
    J Immunol. 2001 Sep 15;167(6):3257-65 PMID: 11544313
  107. Differential requirement for Rel/nuclear factor kappa B family members in natural killer T cell development.
    J Exp Med. 2003 Jun 16;197(12):1613-21 PMID: 12810684
  108. A novel mutation in the Nfkb2 gene generates an NF-kappa B2 "super repressor".
    J Immunol. 2007 Dec 1;179(11):7514-22 PMID: 18025196
  109. A unique lymphotoxin {alpha}beta-dependent pathway regulates thymic emigration of V{alpha}14 invariant natural killer T cells.
    Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9160-5 PMID: 16751279
  110. Differential regulation of c-Rel translocation in activated B and T cells.
    J Immunol. 1996 Aug 1;157(3):1149-55 PMID: 8757620
  111. Rel-dependent induction of A1 transcription is required to protect B cells from antigen receptor ligation-induced apoptosis.
    Genes Dev. 1999 Feb 15;13(4):400-11 PMID: 10049356
  112. CD4(+) CD25(+) regulatory T cell selection.
    Ann N Y Acad Sci. 2004 Dec;1029:101-14 PMID: 15681750
  113. Regulation of secondary lymphoid organ development by the nuclear factor-kappaB signal transduction pathway.
    Immunol Rev. 2003 Oct;195:91-105 PMID: 12969313
  114. Tumor suppressor CYLD: negative regulation of NF-kappaB signaling and more.
    Cell Mol Life Sci. 2008 Apr;65(7-8):1123-32 PMID: 18193168
  115. Synergism between NF-kappa B1/p50 and Notch2 during the development of marginal zone B lymphocytes.
    J Immunol. 2007 Jul 1;179(1):195-200 PMID: 17579038
  116. Regulation of Ig class switch recombination by NF-kappaB: retroviral expression of RelB in activated B cells inhibits switching to IgG1, but not to IgE.
    Int Immunol. 2002 Sep;14(9):983-91 PMID: 12202396
  117. Receptor-specific regulation of B-cell susceptibility to Fas-mediated apoptosis and a novel Fas apoptosis inhibitory molecule.
    Immunol Rev. 2000 Aug;176:116-33 PMID: 11043772
  118. CARMA1 controls an early checkpoint in the thymic development of FoxP3+ regulatory T cells.
    J Immunol. 2009 Jun 1;182(11):6736-43 PMID: 19454668
  119. Thymic development and peripheral homeostasis of regulatory T cells.
    Curr Opin Immunol. 2007 Apr;19(2):176-85 PMID: 17306520
  120. Mature T cells depend on signaling through the IKK complex.
    Immunity. 2003 Sep;19(3):377-89 PMID: 14499113
  121. Thymus development and function.
    Curr Opin Immunol. 2008 Apr;20(2):178-84 PMID: 18403191
  122. Epigenetic ontogeny of the Igk locus during B cell development.
    Nat Immunol. 2005 Feb;6(2):198-203 PMID: 15619624
  123. c-Rel is required for the protection of B cells from antigen receptor-mediated, but not Fas-mediated, apoptosis.
    J Immunol. 2001 Nov 1;167(9):4948-56 PMID: 11673501
  124. NIK-dependent RelB activation defines a unique signaling pathway for the development of V alpha 14i NKT cells.
    J Exp Med. 2003 Jun 16;197(12):1623-33 PMID: 12810685
  125. TAK1 is indispensable for development of T cells and prevention of colitis by the generation of regulatory T cells.
    Int Immunol. 2006 Oct;18(10):1405-11 PMID: 16940043
  126. Differential role of the transcription factor NF-kappaB in selection and survival of CD4+ and CD8+ thymocytes.
    Immunity. 2008 Oct 17;29(4):523-37 PMID: 18957265
  127. NF-kappaB and the immunoglobulin kappa gene enhancer.
    J Exp Med. 2004 Nov 1;200(9):1099-102 PMID: 15520242
  128. Essential role of TAK1 in thymocyte development and activation.
    Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11677-82 PMID: 16857737
  129. T(H)-17 differentiation: of mice and men.
    Nat Immunol. 2007 Sep;8(9):903-5 PMID: 17712339
  130. Requirement for NF-kappaB in osteoclast and B-cell development.
    Genes Dev. 1997 Dec 15;11(24):3482-96 PMID: 9407039
  131. BCR-mediated apoptosis associated with negative selection of immature B cells is selectively dependent on Pten.
    Cell Res. 2009 Feb;19(2):196-207 PMID: 18781138
  132. NF-kappa B RelA-deficient lymphocytes: normal development of T cells and B cells, impaired production of IgA and IgG1 and reduced proliferative responses.
    J Exp Med. 1997 Mar 3;185(5):953-61 PMID: 9120401
  133. NF-kappaB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes.
    Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9136-41 PMID: 10430908
  134. An essential role for nuclear factor kappaB in promoting double positive thymocyte apoptosis.
    J Exp Med. 1999 Jan 4;189(1):145-58 PMID: 9874571
  135. Female mice heterozygous for IKK gamma/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti.
    Mol Cell. 2000 Jun;5(6):969-79 PMID: 10911991
  136. A proximal kappaB site in the IL-23 p19 promoter is responsible for RelA- and c-Rel-dependent transcription.
    J Immunol. 2007 Nov 15;179(10):6596-603 PMID: 17982049
  137. Distinct activities of p52/NF-kappa B required for proper secondary lymphoid organ microarchitecture: functions enhanced by Bcl-3.
    J Immunol. 1999 Dec 15;163(12):6581-8 PMID: 10586052
  138. The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games.
    Immunology. 2005 May;115(1):1-20 PMID: 15819693
  139. Disentangling the MYC web.
    Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5757-9 PMID: 11983876
  140. Rel/NF-kappaB family member RelA regulates NK1.1- to NK1.1+ transition as well as IL-15-induced expansion of NKT cells.
    Eur J Immunol. 2008 Dec;38(12):3508-19 PMID: 19003818
  141. Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells.
    J Biol Chem. 2007 May 25;282(21):15884-93 PMID: 17392286
  142. TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105.
    Nature. 1999 Jan 28;397(6717):363-8 PMID: 9950430
  143. Mapping of a functional recombination motif that defines isotype specificity for mu-->gamma3 switch recombination implicates NF-kappaB p50 as the isotype-specific switching factor.
    J Exp Med. 2004 Mar 1;199(5):617-27 PMID: 14993249
  144. The protean nature of cells in the B lymphocyte lineage.
    Immunity. 2007 Jun;26(6):703-14 PMID: 17582343
  145. Accumulation of marginal zone B cells and accelerated loss of follicular dendritic cells in NF-kappaB p50-deficient mice.
    BMC Immunol. 2005 Apr 18;6:8 PMID: 15836790
  146. I-kappa B kinases alpha and beta have distinct roles in regulating murine T cell function.
    J Immunol. 2002 Apr 15;168(8):3721-31 PMID: 11937522
  147. NF-kappa B binds to the immunoglobulin S gamma 3 region in vivo during class switch recombination.
    Eur J Immunol. 2006 Dec;36(12):3315-23 PMID: 17109470
  148. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family.
    Cell. 1995 Jan 27;80(2):331-40 PMID: 7834753
  149. The combined absence of NF-kappa B1 and c-Rel reveals that overlapping roles for these transcription factors in the B cell lineage are restricted to the activation and function of mature cells.
    Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4514-9 PMID: 11930006
  150. NF-kappaB is dispensable for normal lymphocyte development in bone marrow but required for protection of progenitors from TNFalpha.
    Int Immunol. 2006 May;18(5):653-9 PMID: 16571606
  151. Development and selection of Valpha l4i NKT cells.
    Curr Top Microbiol Immunol. 2007;314:195-212 PMID: 17593662
  152. Crucial role for BAFF-BAFF-R signaling in the survival and maintenance of mature B cells.
    PLoS One. 2009;4(5):e5456 PMID: 19421318
  153. Glucocorticoid-induced TNF receptor expression by T cells is reciprocally regulated by NF-kappaB and NFAT.
    J Immunol. 2008 Oct 15;181(8):5405-13 PMID: 18832697
  154. Lymphoid stroma in the initiation and control of immune responses.
    Immunol Rev. 2008 Aug;224:284-94 PMID: 18759934
  155. Genetic control of cell size.
    Curr Opin Genet Dev. 2000 Oct;10(5):529-35 PMID: 10980431
  156. Lymphotoxin beta receptor induces sequential activation of distinct NF-kappa B factors via separate signaling pathways.
    J Biol Chem. 2003 Apr 4;278(14):12006-12 PMID: 12556537
  157. The c-Rel transcription factor and B-cell proliferation: a deal with the devil.
    Oncogene. 2004 Mar 25;23(13):2275-86 PMID: 14755244
  158. c-Rel is required for chromatin remodeling across the IL-2 gene promoter.
    J Immunol. 2003 Apr 1;170(7):3724-31 PMID: 12646638
  159. Ltbetar signaling does not regulate Aire-dependent transcripts in medullary thymic epithelial cells.
    J Immunol. 2008 Jul 1;181(1):400-7 PMID: 18566406
  160. NF-kappa B activation by the pre-T cell receptor serves as a selective survival signal in T lymphocyte development.
    Immunity. 2000 Nov;13(5):677-89 PMID: 11114380
  161. IL-2 and autoimmune disease.
    Cytokine Growth Factor Rev. 2002 Aug-Oct;13(4-5):369-78 PMID: 12220550
  162. TNF family member B cell-activating factor (BAFF) receptor-dependent and -independent roles for BAFF in B cell physiology.
    J Immunol. 2004 Aug 15;173(4):2245-52 PMID: 15294936
  163. c-Rel is a selective activator of a novel IL-4/CD40 responsive element in the human Ig gamma4 germline promoter.
    Mol Immunol. 2002 Mar;38(11):849-59 PMID: 11922943
  164. BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells.
    Nat Immunol. 2002 Oct;3(10):958-65 PMID: 12352969
  165. Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity, and interleukin-2 expression.
    Genes Dev. 1995 Aug 15;9(16):1965-77 PMID: 7649478
  166. CD4+ and CD8+ T cell survival is regulated differentially by protein kinase Ctheta, c-Rel, and protein kinase B.
    J Immunol. 2007 Mar 1;178(5):2932-9 PMID: 17312138
  167. A fourth IkappaB protein within the NF-kappaB signaling module.
    Cell. 2007 Jan 26;128(2):369-81 PMID: 17254973
  168. Different cytokines induce surface lymphotoxin-alphabeta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches.
    Immunity. 2002 Dec;17(6):823-33 PMID: 12479827
  169. Regulation of T-cell progenitor survival and cell-cycle entry by the pre-T-cell receptor.
    Immunol Rev. 2006 Feb;209:159-69 PMID: 16448541
  170. BAFF activates Akt and Erk through BAFF-R in an IKK1-dependent manner in primary mouse B cells.
    Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12435-8 PMID: 18713867
  171. Regulation of peripheral B cell maturation.
    Cell Immunol. 2006 Feb;239(2):92-102 PMID: 16797504
  172. IkappaB kinase signaling is essential for maintenance of mature B cells.
    J Exp Med. 2002 Sep 16;196(6):743-52 PMID: 12235208
  173. Differential dependence of CD4+CD25+ regulatory and natural killer-like T cells on signals leading to NF-kappaB activation.
    Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4566-71 PMID: 15070758
  174. Generation of peripheral B cells occurs via two spatially and temporally distinct pathways.
    Blood. 2007 Mar 15;109(6):2521-8 PMID: 17105816
  175. NF-kappaB2 is required for the establishment of central tolerance through an Aire-dependent pathway.
    J Clin Invest. 2006 Nov;116(11):2964-71 PMID: 17039258
  176. IkappaB kinase alpha is essential for mature B cell development and function.
    J Exp Med. 2001 Feb 19;193(4):417-26 PMID: 11181694
  177. NF-kappaB1 and c-Rel cooperate to promote the survival of TLR4-activated B cells by neutralizing Bim via distinct mechanisms.
    Blood. 2008 Dec 15;112(13):5063-73 PMID: 18805964
  178. Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses.
    Cell. 1995 Jan 27;80(2):321-30 PMID: 7834752
  179. Characteristics and biological functions of TRAF6.
    Adv Exp Med Biol. 2007;597:72-9 PMID: 17633018
  180. Rapid up-regulation of c-FLIP expression by BCR signaling through the PI3K/Akt pathway inhibits simultaneously induced Fas-mediated apoptosis in murine B lymphocytes.
    Immunol Lett. 2007 Mar 15;109(1):36-46 PMID: 17275920
  181. Molecular orchestration of differentiation and function of regulatory T cells.
    Genes Dev. 2009 Jun 1;23(11):1270-82 PMID: 19487568
  182. Lymphoid organ development: from ontogeny to neogenesis.
    Nat Immunol. 2006 Apr;7(4):344-53 PMID: 16550197
  183. Development and selection of gammadelta T cells.
    Immunol Rev. 2007 Feb;215:15-31 PMID: 17291276
  184. The Rel subunit of NF-kappaB-like transcription factors is a positive and negative regulator of macrophage gene expression: distinct roles for Rel in different macrophage populations.
    EMBO J. 1996 Dec 16;15(24):7099-107 PMID: 9003785
  185. RelB is required for Peyer's patch development: differential regulation of p52-RelB by lymphotoxin and TNF.
    EMBO J. 2003 Jan 2;22(1):121-30 PMID: 12505990
  186. Cutting edge: the ontogeny and function of Va14Ja18 natural T lymphocytes require signal processing by protein kinase C theta and NF-kappa B.
    J Immunol. 2004 Apr 15;172(8):4667-71 PMID: 15067039
  187. Role of Rel-related factors in control of c-myc gene transcription in receptor-mediated apoptosis of the murine B cell WEHI 231 line.
    J Exp Med. 1995 Mar 1;181(3):1169-77 PMID: 7869034
  188. A role for nuclear factor kappa B/rel transcription factors in the regulation of the recombinase activator genes.
    Immunity. 2005 Apr;22(4):519-31 PMID: 15845455
  189. Thymic maturation determines gammadelta T cell function, but not their antigen specificities.
    Curr Opin Immunol. 2009 Apr;21(2):140-5 PMID: 19321327
  190. NF-kappaB couples protein kinase B/Akt signaling to distinct survival pathways and the regulation of lymphocyte homeostasis in vivo.
    J Immunol. 2005 Sep 15;175(6):3790-9 PMID: 16148125
  191. Rel induces interferon regulatory factor 4 (IRF-4) expression in lymphocytes: modulation of interferon-regulated gene expression by rel/nuclear factor kappaB.
    J Exp Med. 2000 Apr 17;191(8):1281-92 PMID: 10770796
  192. B cells as effectors.
    Curr Opin Immunol. 2003 Jun;15(3):354-61 PMID: 12787764
  193. Constitutive alternative NF-kappaB signaling promotes marginal zone B-cell development but disrupts the marginal sinus and induces HEV-like structures in the spleen.
    Blood. 2007 Oct 1;110(7):2381-9 PMID: 17620454
  194. CD27 is a thymic determinant of the balance between interferon-gamma- and interleukin 17-producing gammadelta T cell subsets.
    Nat Immunol. 2009 Apr;10(4):427-36 PMID: 19270712
  195. Bcl-3, a multifaceted modulator of NF-kappaB-mediated gene transcription.
    Immunol Res. 2008;42(1-3):210-8 PMID: 19002607
  196. Molecular and cellular mechanisms of T cell development.
    Cell Mol Life Sci. 2004 Feb;61(3):263-80 PMID: 14770292
  197. Combined deficiency of p50 and cRel in CD4+ T cells reveals an essential requirement for nuclear factor kappaB in regulating mature T cell survival and in vivo function.
    J Exp Med. 2003 Apr 7;197(7):861-74 PMID: 12668645
  198. Abnormal immune function of hemopoietic cells from alymphoplasia (aly) mice, a natural strain with mutant NF-kappa B-inducing kinase.
    J Immunol. 2000 Jul 15;165(2):804-12 PMID: 10878354
  199. E2f3 is critical for normal cellular proliferation.
    Genes Dev. 2000 Mar 15;14(6):690-703 PMID: 10733529
  200. Cyclin E and Bcl-xL cooperatively induce cell cycle progression in c-Rel-/- B cells.
    Oncogene. 2003 Nov 20;22(52):8472-86 PMID: 14627988
  201. Thymic microenvironments for T-cell repertoire formation.
    Adv Immunol. 2008;99:59-94 PMID: 19117532
  202. Critical roles for the Bcl-3 oncoprotein in T cell-mediated immunity, splenic microarchitecture, and germinal center reactions.
    Immunity. 1997 Apr;6(4):479-90 PMID: 9133427
  203. The thymus medulla slowly yields its secrets.
    Ann N Y Acad Sci. 2008 Nov;1143:105-22 PMID: 19076347
  204. Murine c-rel transcription is rapidly induced in T-cells and fibroblasts by mitogenic agents and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate.
    Cell Growth Differ. 1990 Aug;1(8):345-50 PMID: 2278886
  205. Bim and the pro-survival Bcl-2 proteins: opposites attract, ERK repels.
    Cell Cycle. 2007 Sep 15;6(18):2236-40 PMID: 17881896
  206. MALT1 directs B cell receptor-induced canonical nuclear factor-kappaB signaling selectively to the c-Rel subunit.
    Nat Immunol. 2007 Sep;8(9):984-91 PMID: 17660823
  207. Lymphotoxin alpha 1 beta 2: a critical mediator in V alpha 14i NKT cell differentiation.
    Mol Immunol. 2005 Feb;42(4):413-7 PMID: 15607792
  208. CXCL13 production by an established lymph node stromal cell line via lymphotoxin-beta receptor engagement involves the cooperation of multiple signaling pathways.
    Int Immunol. 2009 Apr;21(4):467-76 PMID: 19251935
  209. Lymphoid tissue inducer cells: architects of CD4 immune responses in mice and men.
    Clin Exp Immunol. 2009 Jul;157(1):20-6 PMID: 19659766
  210. The role of Rel/NF-kappaB transcription factors in B lymphocyte survival.
    Semin Immunol. 2003 Jun;15(3):159-66 PMID: 14563114
  211. B cell growth is controlled by phosphatidylinosotol 3-kinase-dependent induction of Rel/NF-kappaB regulated c-myc transcription.
    Mol Cell. 2002 Dec;10(6):1283-94 PMID: 12504005
  212. NF-kappa B-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner.
    J Immunol. 2004 Feb 15;172(4):2067-75 PMID: 14764671
  213. The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritis.
    Arthritis Res Ther. 2008;10(4):212 PMID: 18771589
  214. Protein kinase C-theta is required for efficient positive selection.
    J Immunol. 2008 Oct 1;181(7):4696-708 PMID: 18802072
  215. Cracking the BAFF code.
    Nat Rev Immunol. 2009 Jul;9(7):491-502 PMID: 19521398
  216. NF-kappa B controls cell fate specification, survival, and molecular differentiation of immunoregulatory natural T lymphocytes.
    J Immunol. 2004 Feb 15;172(4):2265-73 PMID: 14764695
  217. Shared principles in NF-kappaB signaling.
    Cell. 2008 Feb 8;132(3):344-62 PMID: 18267068
  218. The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator.
    Immunity. 2008 Sep 19;29(3):438-50 PMID: 18799150
  219. NF-kappaB activity marks cells engaged in receptor editing.
    J Exp Med. 2009 Aug 3;206(8):1803-16 PMID: 19581408
  220. Bcl10/Malt1 signaling is essential for TCR-induced NF-kappaB activation in thymocytes but dispensable for positive or negative selection.
    J Immunol. 2007 Jan 15;178(2):953-60 PMID: 17202357
  221. Activation of NF-kappaB promotes the transition of large, CD43+ pre-B cells to small, CD43- pre-B cells.
    Int Immunol. 2005 Jun;17(6):815-25 PMID: 15908447
  222. IKKbeta is essential for protecting T cells from TNFalpha-induced apoptosis.
    Immunity. 2001 Mar;14(3):217-30 PMID: 11290332
  223. Peripheral B cell subsets.
    Curr Opin Immunol. 2008 Apr;20(2):149-57 PMID: 18434123
  224. The anti-apoptotic activities of Rel and RelA required during B-cell maturation involve the regulation of Bcl-2 expression.
    EMBO J. 2000 Dec 1;19(23):6351-60 PMID: 11101508
  225. NF-kappaB/p50 and NF-kappaB/c-Rel differentially regulate the activity of the 3'alphaE-hsl,2 enhancer in normal murine B cells in an activation-dependent manner.
    Int Immunol. 2000 Aug;12(8):1167-72 PMID: 10917891
  226. Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance.
    J Exp Med. 2008 Nov 24;205(12):2827-38 PMID: 19015306
  227. Marginal zone B cells in lymphocyte activation and regulation.
    Curr Opin Immunol. 2005 Jun;17(3):244-50 PMID: 15886113
  228. Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity.
    Immunity. 2008 Sep 19;29(3):451-63 PMID: 18799151
  229. NF-kappa B is required for the positive selection of CD8+ thymocytes.
    J Immunol. 2000 Nov 1;165(9):5004-10 PMID: 11046028
  230. Involvement of lymphoid inducer cells in the development of secondary and tertiary lymphoid structure.
    BMB Rep. 2009 Apr 30;42(4):189-93 PMID: 19403040
Article Info
Journal
Cold Spring Harbor perspectives in biology
Abbr.
Cold Spring Harb Perspect Biol
ISSN
1943-0264
DOI
10.1101/cshperspect.a000182
Email
gerondakis@burnet.edu.au
Published
2010-05-00
Epub
2009-00-23
Pages
a000182
Language
English
Region
United States
NLM ID
101513680
PMCID
PMC2857169
Subset
IM
External Links
PubMed source DOI: 10.1101/cshperspect.a000182 PMC Full Text View journal details
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