Gene Symbol: Relb
Description: avian reticuloendotheliosis viral (v-rel) oncogene related B
Alias: shep, transcription factor RelB
Species: mouse
Products:     Relb

Top Publications

  1. Guo F, Tänzer S, Busslinger M, Weih F. Lack of nuclear factor-kappa B2/p100 causes a RelB-dependent block in early B lymphopoiesis. Blood. 2008;112:551-9 pubmed publisher a block of early B-cell development at the transition from the pre-pro-B to the pro-B-cell stage due to enhanced RelB activity...
  2. Weih F, Caamano J. Regulation of secondary lymphoid organ development by the nuclear factor-kappaB signal transduction pathway. Immunol Rev. 2003;195:91-105 pubmed
    ..that activation of the recently described alternative NF-kappaB pathway by membrane-bound lymphotoxin, via p52-RelB heterodimers, plays a major role during initiation steps of secondary lymphoid organ development...
  3. Doi T, Marino M, Takahashi T, Yoshida T, Sakakura T, Old L, et al. Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic lethality. Proc Natl Acad Sci U S A. 1999;96:2994-9 pubmed
    ..Thus, the RelA-mediated antiapoptotic signal that protects normal cells from TNF injury in vitro can be shown to be operative in vivo. ..
  4. Ryseck R, Bull P, Takamiya M, Bours V, Siebenlist U, Dobrzanski P, et al. RelB, a new Rel family transcription activator that can interact with p50-NF-kappa B. Mol Cell Biol. 1992;12:674-84 pubmed
    We have identified a serum-inducible gene, relB, which encodes a protein of 558 amino acids containing a region with high similarity to c-Rel and other members of the Rel family...
  5. Lovas A, Radke D, Albrecht D, Yilmaz Z, Möller U, Habenicht A, et al. Differential RelA- and RelB-dependent gene transcription in LTbetaR-stimulated mouse embryonic fibroblasts. BMC Genomics. 2008;9:606 pubmed publisher
    ..and the alternative p100-regulated pathway that result in the activation of p50-RelA and p52-RelB NF-kappaB heterodimers, respectively...
  6. Zuklys S, Balciunaite G, Agarwal A, Fasler Kan E, Palmer E, Hollander G. Normal thymic architecture and negative selection are associated with Aire expression, the gene defective in the autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). J Immunol. 2000;165:1976-83 pubmed
    ..Early during development, thymic Aire transcription is critically dependent on RelB and occurs in epithelial cells in response to lymphocyte-mediated signals...
  7. Gray D, Seach N, Ueno T, Milton M, Liston A, Lew A, et al. Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood. 2006;108:3777-85 pubmed
    ..of adult epithelium were studied, using various mutant mice to demonstrate new cross talk checkpoints dependent on RelB in the cortex and CD40 in the medulla...
  8. Akiyama T, Shimo Y, Yanai H, Qin J, Ohshima D, Maruyama Y, et al. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity. 2008;29:423-37 pubmed publisher
    ..These results show that developmental-stage-dependent cooperation between RANK and CD40 promotes mTEC development, thereby establishing self-tolerance. ..
  9. Otero J, Dai S, Alhawagri M, Darwech I, Abu Amer Y. IKKbeta activation is sufficient for RANK-independent osteoclast differentiation and osteolysis. J Bone Miner Res. 2010;25:1282-94 pubmed publisher
    ..NF-kappaB p100 and p105, but not RelB, were critical mediators of this effect...

More Information


  1. DeKoning J, DiMolfetto L, Reilly C, Wei Q, Havran W, Lo D. Thymic cortical epithelium is sufficient for the development of mature T cells in relB-deficient mice. J Immunol. 1997;158:2558-66 pubmed
    ..As relB-deficient mice appear to lack thymic medullary epithelium and mature dendritic cells, we studied the effect of this ..
  2. Roberts N, White A, Jenkinson W, Turchinovich G, Nakamura K, Withers D, et al. Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium. Immunity. 2012;36:427-37 pubmed publisher
  3. Weih F, Durham S, Barton D, Sha W, Baltimore D, Bravo R. Both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent. J Immunol. 1996;157:3974-9 pubmed
    Mice with a targeted disruption of RelB, a member of the Rel/NF-kappaB family of transcription factors, have multifocal, mixed inflammatory cell infiltration in several organs, myeloid hyperplasia, and splenomegaly due to extramedullary ..
  4. Müller J, Siebenlist U. Lymphotoxin beta receptor induces sequential activation of distinct NF-kappa B factors via separate signaling pathways. J Biol Chem. 2003;278:12006-12 pubmed
    ..NF-kappaB2 p100 precursor protein to the p52 form and resulted in a delayed but sustained activation of primarily RelB-containing NF-kappaB dimers...
  5. Naspetti M, Aurrand Lions M, DeKoning J, Malissen M, Galland F, Lo D, et al. Thymocytes and RelB-dependent medullary epithelial cells provide growth-promoting and organization signals, respectively, to thymic medullary stromal cells. Eur J Immunol. 1997;27:1392-7 pubmed
    ..In RelB-deficient mice, T cell maturation proceeds normally but negative selection is inefficient due to the lack of thymic ..
  6. Carrasco D, Ryseck R, Bravo R. Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells. Development. 1993;118:1221-31 pubmed
    We have studied the expression of the relB gene during mouse development using in situ hybridization and immunocytochemical analysis...
  7. Fusco A, Huang D, Miller D, Wang V, Vu D, Ghosh G. NF-kappaB p52:RelB heterodimer recognizes two classes of kappaB sites with two distinct modes. EMBO Rep. 2009;10:152-9 pubmed publisher
    The X-ray structure of the nuclear factor-kappaB (NF-kappaB) p52:RelB:kappaB DNA complex reveals a new recognition feature not previously seen in other NF-kappaB:kappaB DNA complexes...
  8. Baeuerle P, Baltimore D. NF-kappa B: ten years after. Cell. 1996;87:13-20 pubmed
  9. Sasaki C, Ghosh P, Longo D. Recruitment of RelB to the Csf2 promoter enhances RelA-mediated transcription of granulocyte-macrophage colony-stimulating factor. J Biol Chem. 2011;286:1093-102 pubmed publisher
    ..The synergistic effect of LT? priming was not observed with other TNF-responsive genes such as Ccl2 or RelB, which suggested that this effect was not a general increase in TNF signaling...
  10. Heino M, Peterson P, Sillanpää N, Guerin S, Wu L, Anderson G, et al. RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur J Immunol. 2000;30:1884-93 pubmed
    ..We also demonstrate that the Aire protein is absent in the thymus of RelB-deficient mouse and in NOD thymus most of the Aire positive cells showed an abnormal morphology...
  11. Weih F, Carrasco D, Bravo R. Constitutive and inducible Rel/NF-kappa B activities in mouse thymus and spleen. Oncogene. 1994;9:3289-97 pubmed
    ..Although RelB protein is present at significantly lower levels in thymus and spleen extracts when compared to RelA, in both ..
  12. Yilmaz Z, Weih D, Sivakumar V, Weih F. RelB is required for Peyer's patch development: differential regulation of p52-RelB by lymphotoxin and TNF. EMBO J. 2003;22:121-30 pubmed
    Targeted disruption of the Rel/NF-kappaB family members NF-kappaB2, encoding p100/p52, and RelB in mice results in anatomical defects of secondary lymphoid tissues...
  13. Barton D, HogenEsch H, Weih F. Mice lacking the transcription factor RelB develop T cell-dependent skin lesions similar to human atopic dermatitis. Eur J Immunol. 2000;30:2323-32 pubmed
    Mice with a targeted disruption of the Rel / NF-kappaB family member RelB develop a complex inflammatory phenotype and hematopoietic abnormalities...
  14. Burkly L, Hession C, Ogata L, Reilly C, Marconi L, Olson D, et al. Expression of relB is required for the development of thymic medulla and dendritic cells. Nature. 1995;373:531-6 pubmed
    ..has not been defined at a molecular level, but recent studies have shown an association between expression of the relB subunit of the NF-kappa B complex and the presence of DC in specific regions of normal unstimulated lymphoid ..
  15. Xia Y, Chen S, Wang Y, Mackman N, Ku G, Lo D, et al. RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts. Mol Cell Biol. 1999;19:7688-96 pubmed
    Members of the NF-kappaB/RelB family of transcription factors play important roles in the regulation of inflammatory and immune responses...
  16. Naquet P, Naspetti M, Boyd R. Development, organization and function of the thymic medulla in normal, immunodeficient or autoimmune mice. Semin Immunol. 1999;11:47-55 pubmed
    ..These signals are lacking in RelB-deficient mice leading to the disorganization of the corticomedullary junction and abnormal negative selection ..
  17. Lo D, Quill H, Burkly L, Scott B, Palmiter R, Brinster R. A recessive defect in lymphocyte or granulocyte function caused by an integrated transgene. Am J Pathol. 1992;141:1237-46 pubmed
    ..Because tissue development and morphology appears to be normal in all other tissues observed, the genetic lesion appears to specifically affect the regulation of lymphocyte or granulocyte activation. ..
  18. Akiyama T, Maeda S, Yamane S, Ogino K, Kasai M, Kajiura F, et al. Dependence of self-tolerance on TRAF6-directed development of thymic stroma. Science. 2005;308:248-51 pubmed
    ..Engraftment of thymic stroma of TRAF6(-/-) embryos into athymic nude mice induced autoimmunity. Thus, TRAF6 directs the development of thymic stroma and represents a critical point of regulation for self-tolerance and autoimmunity. ..
  19. Vaira S, Johnson T, Hirbe A, Alhawagri M, Anwisye I, Sammut B, et al. RelB is the NF-kappaB subunit downstream of NIK responsible for osteoclast differentiation. Proc Natl Acad Sci U S A. 2008;105:3897-902 pubmed publisher
    ..deletion of p100 restores the capacity of NIK-deficient osteoclast (OC) precursors to differentiate and normalizes RelB and p65 signaling. Differentiation of NIK-/- precursors is also restored by overexpression of RelB, but not p65...
  20. Snapper C, Rosas F, Zelazowski P, Moorman M, Kehry M, Bravo R, et al. B cells lacking RelB are defective in proliferative responses, but undergo normal B cell maturation to Ig secretion and Ig class switching. J Exp Med. 1996;184:1537-41 pubmed
    ..b>RelB, another member of the NF-kappa B/Rel family of transcription factors, is expressed during the latter stages of B ..
  21. Gerondakis S, Grossmann M, Nakamura Y, Pohl T, Grumont R. Genetic approaches in mice to understand Rel/NF-kappaB and IkappaB function: transgenics and knockouts. Oncogene. 1999;18:6888-95 pubmed
    ..Future studies will no doubt focus on the effect of multiple gene disruptions of members of this signaling pathway, on tissue-specific disruptions of these genes, and on the use of these mice as models for human diseases. ..
  22. Wu L, D Amico A, Winkel K, Suter M, Lo D, Shortman K. RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity. 1998;9:839-47 pubmed
    The transcription factor RelB had been shown to be important for dendritic cell (DC) development, but the type of DC involved was not clear...
  23. Weih F, Durham S, Barton D, Sha W, Baltimore D, Bravo R. p50-NF-kappaB complexes partially compensate for the absence of RelB: severely increased pathology in p50(-/-)relB(-/-) double-knockout mice. J Exp Med. 1997;185:1359-70 pubmed
    b>RelB-deficient mice (relB(-/-)) have a complex phenotype including multiorgan inflammation and hematopoietic abnormalities...
  24. Ripen A, Nitta T, Murata S, Tanaka K, Takahama Y. Ontogeny of thymic cortical epithelial cells expressing the thymoproteasome subunit ?5t. Eur J Immunol. 2011;41:1278-87 pubmed publisher
    ..5 mouse embryos. We also found that ?5t expression in cTECs was detectable in mice deficient for RelB or Rag2, indicating that ?5t in cTECs is expressed in the absence of thymic medulla formation or thymocyte ..
  25. Weih F, Warr G, Yang H, Bravo R. Multifocal defects in immune responses in RelB-deficient mice. J Immunol. 1997;158:5211-8 pubmed
    Mice with a targeted disruption of the Rel/nuclear factor-kappaB family member RelB develop a complex inflammatory phenotype, myeloid hyperplasia, and splenomegaly due to extramedullary hemopoiesis...
  26. Guo F, Weih D, Meier E, Weih F. 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;110:2381-9 pubmed
    ..Thus, constitutive activation of the alternative NF-kappaB pathway favors MZ B-cell development and accumulation but leads to a disorganized spleen microarchitecture. ..
  27. Bonizzi G, Bebien M, Otero D, Johnson Vroom K, Cao Y, Vu D, et al. Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers. EMBO J. 2004;23:4202-10 pubmed
    ..NF-kappaB signaling pathway based on processing of the NF-kappaB2/p100 precursor protein, which associates with RelB in the cytoplasm...
  28. Kobayashi T, Walsh P, Walsh M, Speirs K, Chiffoleau E, King C, et al. TRAF6 is a critical factor for dendritic cell maturation and development. Immunity. 2003;19:353-63 pubmed
    ..Together these results indicate that TRAF6 regulates the critical processes required for maturation, activation, and development of DCs, the primary cellular bridge between innate and adaptive immunity. ..
  29. Demicco E, Kavanagh K, Romieu Mourez R, Wang X, Shin S, Landesman Bollag E, et al. RelB/p52 NF-kappaB complexes rescue an early delay in mammary gland development in transgenic mice with targeted superrepressor IkappaB-alpha expression and promote carcinogenesis of the mammary gland. Mol Cell Biol. 2005;25:10136-47 pubmed
    ..5). Recovery correlated with induction of nuclear cyclin D1 and RelB/p52 NF-kappaB complexes...
  30. Derudder E, Dejardin E, Pritchard L, Green D, Korner M, Baud V. RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100. J Biol Chem. 2003;278:23278-84 pubmed
    ..We demonstrate that LTbetaR ligation induces not only RelA/p50 dimers but also RelB/p50 dimers, whereas TNF-alpha induces only RelA/p50 dimers...
  31. Weih D, Yilmaz Z, Weih F. Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines. J Immunol. 2001;167:1909-19 pubmed
    High levels of the Rel/NF-kappaB family member RelB are restricted to specific regions of thymus, lymph nodes, and Peyer's patches...
  32. Weih F, Carrasco D, Durham S, Barton D, Rizzo C, Ryseck R, et al. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell. 1995;80:331-40 pubmed
    b>RelB, a member of the NF-kappa B/Rel family of transcription factors, has been implicated in the constitutive expression of kappa B-regulated genes in lymphoid tissues...
  33. Li J, Li Y, Yao J, Jin R, Zhu M, Qian X, et al. Developmental pathway of CD4+CD8- medullary thymocytes during mouse ontogeny and its defect in Aire-/- mice. Proc Natl Acad Sci U S A. 2007;104:18175-80 pubmed
    ..medulla seemed to be critically dependent on a functionally intact medullary epithelial cell compartment because Relb and Aire deficiency were found to cause severe blockage at the transition from SP3 to SP4...
  34. Dobrzanski P, Ryseck R, Bravo R. Both N- and C-terminal domains of RelB are required for full transactivation: role of the N-terminal leucine zipper-like motif. Mol Cell Biol. 1993;13:1572-82 pubmed
    b>RelB, a member of the Rel family of transcription factors, can stimulate promoter activity in the presence of p50-NF-kappa B or p50B/p49-NF-kappa B in mammalian cells...
  35. Shih V, Davis Turak J, Macal M, Huang J, Ponomarenko J, Kearns J, et al. Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-?B pathways. Nat Immunol. 2012;13:1162-70 pubmed publisher
    The NF-?B protein RelB controls dendritic cell (DC) maturation and may be targeted therapeutically to manipulate T cell responses in disease...
  36. Muggia A, Teesalu T, Neri A, Blasi F, Talarico D. Trophoblast giant cells express NF-kappa B2 during early mouse development. Dev Genet. 1999;25:23-30 pubmed
    ..could play a role in early mammalian development, we have analyzed the expression of nfkb1, nfkb2, c-Rel, RelA, RelB, and bcl-3 from 6.5- to 10.5-day mouse embryo implantation sites...
  37. Vogel C, Matsumura F. A new cross-talk between the aryl hydrocarbon receptor and RelB, a member of the NF-kappaB family. Biochem Pharmacol. 2009;77:734-45 pubmed publisher
    The discovery of the new crosstalk between the aryl hydrocarbon receptor (AhR) and the NF-kappaB subunit RelB may extend our understanding of the biological functions of the AhR and at the same time raises a number of questions, which ..
  38. Cui C, Hashimoto T, Grivennikov S, Piao Y, Nedospasov S, Schlessinger D. Ectodysplasin regulates the lymphotoxin-beta pathway for hair differentiation. Proc Natl Acad Sci U S A. 2006;103:9142-7 pubmed
    ..The fourth pathway was unexpected, a variant NF-kappaB-signaling cascade based on lymphotoxin-beta (LTbeta)/RelB. Previously known to participate only in lymphoid organogenesis, LTbeta was enriched in developing hair follicles ..
  39. Otero J, Chen T, Zhang K, Abu Amer Y. Constitutively active canonical NF-?B pathway induces severe bone loss in mice. PLoS ONE. 2012;7:e38694 pubmed publisher
    ..Mechanistically, we observed that IKK2SSEE induced high expression of not only p65 but also p52 and RelB; the latter two molecules are considered exclusive members of the alternative NF-?B pathway...
  40. Schmidt Ullrich R, Memet S, Lilienbaum A, Feuillard J, Raphael M, Israel A. NF-kappaB activity in transgenic mice: developmental regulation and tissue specificity. Development. 1996;122:2117-28 pubmed
    ..Considering the results of the p50, p65, relB and c-rel knock-out mice and our present findings, we believe that the NF-kappaB/Rel proteins known so far are ..
  41. Wu H, Lo Y, Chan A, Law K, Mok M. Rel B-modified dendritic cells possess tolerogenic phenotype and functions on lupus splenic lymphocytes in vitro. Immunology. 2016;149:48-61 pubmed publisher
    ..We used lentiviral transduction of RelB-silencing short hairpin RNA to modify the expression of RelB, a key transcription factor regulating DC maturation, ..
  42. Kong S, Dong H, Song J, Thiruppathi M, Prabhakar B, Qiu Q, et al. Deleted in Breast Cancer 1 Suppresses B Cell Activation through RelB and Is Regulated by IKKα Phosphorylation. J Immunol. 2015;195:3685-93 pubmed publisher
    ..Using a double mutant genetic model, we confirm that DBC1 suppresses B cell activation through RelB inhibition...
  43. Bautista D, Wilson S, Hoon M. Why we scratch an itch: the molecules, cells and circuits of itch. Nat Neurosci. 2014;17:175-82 pubmed publisher
    ..Understanding the itch circuitry is critical to developing new therapies for this intractable disease. ..
  44. Eigenbrod T, Bode K, Dalpke A. Early inhibition of IL-1? expression by IFN-? is mediated by impaired binding of NF-?B to the IL-1? promoter but is independent of nitric oxide. J Immunol. 2013;190:6533-41 pubmed publisher
    ..The findings provide evidence for a rapid immune-modulating effect of IFN-? independent of NO...
  45. Cowan J, Parnell S, Nakamura K, Caamano J, Lane P, Jenkinson E, et al. The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development. J Exp Med. 2013;210:675-81 pubmed publisher
    ..conventional CD69(+)Qa2(-) CD4 single-positive thymocytes mature to the late CD69(-)Qa2(+) stage in the absence of RelB-dependent medullary thymic epithelial cells (mTECs)...
  46. Luo L, Sun Z, Fang Q, Huang S, Bai X, Luo G. Effects of tolerogenic dendritic cells generated by siRNA-mediated RelB silencing on immune defense and surveillance functions of T cells. Cell Immunol. 2013;282:28-37 pubmed publisher
    ..In this study, we inhibited RelB expression in immature (im)DCs using small interfering RNA (siRNA) to maintain their immature status...
  47. White A, Jenkinson W, Cowan J, Parnell S, Bacon A, Jones N, et al. An essential role for medullary thymic epithelial cells during the intrathymic development of invariant NKT cells. J Immunol. 2014;192:2659-66 pubmed publisher
    ..Moreover, the identification of a novel requirement for iNKT cells in thymus medulla development further highlights the role of both innate and adaptive immune cells in thymus medulla formation. ..
  48. Qin J, Konno H, Ohshima D, Yanai H, Motegi H, Shimo Y, et al. 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;179:6799-807 pubmed
    ..These data suggest that developmentally regulated activation of TRAF6 in FDCs is required for inducing CXCL13 expression to maintain B cell follicles. ..
  49. Ishimaru N, Kishimoto H, Hayashi Y, Sprent J. Regulation of naive T cell function by the NF-kappaB2 pathway. Nat Immunol. 2006;7:763-72 pubmed
    ..The function of the 'nonclassical' NF-kappaB2-RelB pathway is less clear, although T cells lacking components of this pathway have activation defects...
  50. Zhu B, Yang L, Zhao X, Jiang H, Zhu L. [RNA interference of RelB enhances the radiosensitivity of prostate cancer cell line RM-1 in mice]. Zhonghua Nan Ke Xue. 2012;18:595-9 pubmed
    To investigate the effect of RNA interference of the RelB gene on the radiosensitivity of the mouse prostate cancer cell line RM-1 and its mechanism...
  51. Oldstone M, Race R, Thomas D, Lewicki H, Homann D, Smelt S, et al. Lymphotoxin-alpha- and lymphotoxin-beta-deficient mice differ in susceptibility to scrapie: evidence against dendritic cell involvement in neuroinvasion. J Virol. 2002;76:4357-63 pubmed
  52. Sivakumar V, Hammond K, Howells N, Pfeffer K, Weih F. Differential requirement for Rel/nuclear factor kappa B family members in natural killer T cell development. J Exp Med. 2003;197:1613-21 pubmed
    ..1-positive NKT cells. The Rel/NF-kappa B family member RelB, on the other hand, had to be expressed in radiation resistant thymic stromal cells for the generation of early NK-..
  53. Castiglioni P, Hall D, Jacovetty E, Ingulli E, Zanetti M. Protection against influenza A virus by memory CD8 T cells requires reactivation by bone marrow-derived dendritic cells. J Immunol. 2008;180:4956-64 pubmed
    ..In this study, using relB(-/-) mice we began to investigate the role of bone marrow (BM)-derived dendritic cells (DCs) in the mechanism of ..