Regulation of B-cell Function by NF-kappaB C-Rel in Health and Disease

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2020 Mar 5

PMID 32130429

Citations 9

Authors

Shrikanth C Basavarajappa

Parameswaran Ramakrishnan

Affiliations

Soon will be listed here.

Abstract

B cells mediate humoral immune response and contribute to the regulation of cellular immune response. Members of the Nuclear Factor kappaB (NF-κB) family of transcription factors play a major role in regulating B-cell functions. NF-κB subunit c-Rel is predominantly expressed in lymphocytes, and in B cells, it is required for survival, proliferation, and antibody production. Dysregulation of c-Rel expression and activation alters B-cell homeostasis and is associated with B-cell lymphomas and autoimmune pathologies. Based on its essential roles, c-Rel may serve as a potential prognostic and therapeutic target. This review summarizes the current understanding of the multifaceted role of c-Rel in B cells and B-cell diseases.

Citing Articles

NFκB signalling in colorectal cancer: Examining the central dogma of IKKα and IKKβ signalling.

McKenzie M, Lian G, Pennel K, Quinn J, Jamieson N, Edwards J Heliyon. 2024; 10(12):e32904.

PMID: 38975078 PMC: 11226910. DOI: 10.1016/j.heliyon.2024.e32904.

Transient interactions modulate the affinity of NF-κB transcription factors for DNA.

Li T, Shahabi S, Biswas T, Tsodikov O, Pan W, Huang D Proc Natl Acad Sci U S A. 2024; 121(23):e2405555121.

PMID: 38805268 PMC: 11161749. DOI: 10.1073/pnas.2405555121.

Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells.

Farhana A, Alsrhani A, Alghsham R, Derafa W, Khan Y, Rasheed Z Int J Mol Sci. 2024; 25(3).

PMID: 38338683 PMC: 10855246. DOI: 10.3390/ijms25031404.

Serum sCD25/ferritin ratio combined with MCP-1 is a valid predictor for identifying LAHS with HLH as the first manifestation.

Zou H, He L, Hue Z, Liu M, Yao S, Zhu Y J Cancer Res Clin Oncol. 2023; 149(11):8521-8533.

PMID: 37093345 DOI: 10.1007/s00432-023-04781-4.

Bioinformatics Analysis of miRNAs Targeting TRAF5 in DLBCL Involving in NF-B Signaling Pathway and Affecting the Apoptosis and Signal Transduction.

Li C, Huang L, Wen Y, Yi M, Gao M Genet Res (Camb). 2023; 2022:3222253.

PMID: 36619898 PMC: 9803564. DOI: 10.1155/2022/3222253.

References

Sleckman B, Gorman J, Alt F . Accessibility control of antigen-receptor variable-region gene assembly: role of cis-acting elements. Annu Rev Immunol. 1996; 14:459-81. DOI: 10.1146/annurev.immunol.14.1.459. View

Chang M, Jin W, Chang J, Xiao Y, Brittain G, Yu J . The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity. Nat Immunol. 2011; 12(10):1002-9. PMC: 3178748. DOI: 10.1038/ni.2090. View

Chang M, Jin W, Sun S . Peli1 facilitates TRIF-dependent Toll-like receptor signaling and proinflammatory cytokine production. Nat Immunol. 2009; 10(10):1089-95. PMC: 2748822. DOI: 10.1038/ni.1777. View

Hunter J, Butterworth J, Zhao B, Sellier H, Campbell K, Thomas H . The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma. Oncogene. 2015; 35(26):3476-84. PMC: 4853301. DOI: 10.1038/onc.2015.399. View

Barth T, Joos S, Menz C, Hasel C, Mechtersheimer G, Parwaresch R . Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma. Blood. 2003; 101(9):3681-6. DOI: 10.1182/blood-2002-08-2577. View

Jain A, Ma C, Liu S, Brown M, Cohen J, Strober W . Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia. Nat Immunol. 2001; 2(3):223-8. DOI: 10.1038/85277. View

Lin S, Wortis H, Stavnezer J . The ability of CD40L, but not lipopolysaccharide, to initiate immunoglobulin switching to immunoglobulin G1 is explained by differential induction of NF-kappaB/Rel proteins. Mol Cell Biol. 1998; 18(9):5523-32. PMC: 109137. DOI: 10.1128/MCB.18.9.5523. View

Chin M, Herscovitch M, Zhang N, Waxman D, Gilmore T . Overexpression of an activated REL mutant enhances the transformed state of the human B-lymphoma BJAB cell line and alters its gene expression profile. Oncogene. 2009; 28(20):2100-11. PMC: 2796798. DOI: 10.1038/onc.2009.74. View

OReilly L, Hughes P, Lin A, Waring P, Siebenlist U, Jain R . Loss of c-REL but not NF-κB2 prevents autoimmune disease driven by FasL mutation. Cell Death Differ. 2014; 22(5):767-78. PMC: 4392074. DOI: 10.1038/cdd.2014.168. View

10.

Milanovic M, Heise N, De Silva N, Anderson M, Silva K, Carette A . Differential requirements for the canonical NF-κB transcription factors c-REL and RELA during the generation and activation of mature B cells. Immunol Cell Biol. 2016; 95(3):261-271. PMC: 5360551. DOI: 10.1038/icb.2016.95. View

11.

Barth T, Bentz M, Leithauser F, Stilgenbauer S, Siebert R, Schlotter M . Molecular-cytogenetic comparison of mucosa-associated marginal zone B-cell lymphoma and large B-cell lymphoma arising in the gastro-intestinal tract. Genes Chromosomes Cancer. 2001; 31(4):316-25. DOI: 10.1002/gcc.1150. View

12.

Kaku H, Horikawa K, Obata Y, Kato I, Okamoto H, Sakaguchi N . NF-kappaB is required for CD38-mediated induction of C(gamma)1 germline transcripts in murine B lymphocytes. Int Immunol. 2002; 14(9):1055-64. DOI: 10.1093/intimm/dxf072. View

13.

Vazquez M, Catalan-Dibene J, Zlotnik A . B cells responses and cytokine production are regulated by their immune microenvironment. Cytokine. 2015; 74(2):318-26. PMC: 4475485. DOI: 10.1016/j.cyto.2015.02.007. View

14.

Li L, Xu-Monette Z, Ok C, Tzankov A, Manyam G, Sun R . Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma. Oncotarget. 2015; 6(27):23157-80. PMC: 4695110. DOI: 10.18632/oncotarget.4319. View

15.

Morgan M, Liu Z . Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res. 2010; 21(1):103-15. PMC: 3193400. DOI: 10.1038/cr.2010.178. View

16.

Wu J, Chiang M, Hsu P, Tsai D, Hung K, Wang Y . O-GlcNAcylation is required for B cell homeostasis and antibody responses. Nat Commun. 2017; 8(1):1854. PMC: 5707376. DOI: 10.1038/s41467-017-01677-z. View

17.

Gilmore T, Cormier C, Jean-Jacques J, Gapuzan M . Malignant transformation of primary chicken spleen cells by human transcription factor c-Rel. Oncogene. 2001; 20(48):7098-103. DOI: 10.1038/sj.onc.1204898. View

18.

Fisher G, Rosenberg F, Straus S, DALE J, Middleton L, Lin A . Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995; 81(6):935-46. DOI: 10.1016/0092-8674(95)90013-6. View

19.

Gilmore T, Gerondakis S . The c-Rel Transcription Factor in Development and Disease. Genes Cancer. 2011; 2(7):695-711. PMC: 3218406. DOI: 10.1177/1947601911421925. View

20.

Pomerantz J, Baltimore D . Two pathways to NF-kappaB. Mol Cell. 2002; 10(4):693-5. DOI: 10.1016/s1097-2765(02)00697-4. View