NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells

de Valle et al. show that, with age, NFκB1-deficient B cells spontaneously secrete IL-6 and cause a multiorgan autoimmune disease.

[1]  C. Hunter,et al.  IL-6 as a keystone cytokine in health and disease , 2015, Nature Immunology.

[2]  Caroline L. Wilson,et al.  NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma , 2015, Nature Communications.

[3]  H. Ueno,et al.  Pathophysiology of T follicular helper cells in humans and mice , 2015, Nature Immunology.

[4]  R. Weichselbaum,et al.  Loss of Nfkb1 leads to early onset aging , 2014, Aging.

[5]  U. Klein,et al.  Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits , 2014, The Journal of experimental medicine.

[6]  Laura C. Greaves,et al.  Chronic inflammation induces telomere dysfunction and accelerates ageing in mice , 2014, Nature Communications.

[7]  A. Hoffmann,et al.  IκBε Is a Key Regulator of B Cell Expansion by Providing Negative Feedback on cRel and RelA in a Stimulus-Specific Manner , 2014, The Journal of Immunology.

[8]  J. Caamaño,et al.  Signaling mediated by the NF-κB sub-units NF-κB1, NF-κB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice , 2013, Oncogene.

[9]  A. Hoffmann,et al.  FlowMax: A Computational Tool for Maximum Likelihood Deconvolution of CFSE Time Courses , 2013, PloS one.

[10]  K. J. Henley,et al.  Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease , 2013, Proceedings of the National Academy of Sciences.

[11]  S. Rose-John.  IL-6 Trans-Signaling via the Soluble IL-6 Receptor: Importance for the Pro-Inflammatory Activities of IL-6 , 2012, International journal of biological sciences.

[12]  Stéphane Chevrier,et al.  B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1 , 2012, The Journal of experimental medicine.

[13]  G. Besra,et al.  Human and Mouse Type I Natural Killer T Cell Antigen Receptors Exhibit Different Fine Specificities for CD1d-Antigen Complex* , 2012, The Journal of Biological Chemistry.

[14]  K. Basso,et al.  Roles of BCL6 in normal and transformed germinal center B cells , 2012, Immunological reviews.

[15]  L. Staudt,et al.  Pathogenesis of human B cell lymphomas. , 2012, Annual review of immunology.

[16]  R. Sen,et al.  NF‐κB function in B lymphocytes , 2012, Immunological reviews.

[17]  S. Rose-John,et al.  Transsignaling of Interleukin-6 Crucially Contributes to Atherosclerosis in Mice , 2012, Arteriosclerosis, thrombosis, and vascular biology.

[18]  A. Strasser,et al.  The NF‐κB1 transcription factor prevents the intrathymic development of CD8 T cells with memory properties , 2012, The EMBO journal.

[19]  S. Pillai,et al.  B cells and autoimmunity. , 2011, Current opinion in immunology.

[20]  S. Crotty,et al.  Follicular helper CD4 T cells (TFH). , 2011, Annual review of immunology.

[21]  S. Ghosh,et al.  NF-κB in immunobiology , 2011, Cell Research.

[22]  Michael Meyer-Hermann,et al.  Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter , 2010, Cell.

[23]  S. Kaech,et al.  In Vivo Regulation of Bcl6 and T Follicular Helper Cell Development , 2010, The Journal of Immunology.

[24]  M. Cook,et al.  Dysregulation of germinal centres in autoimmune disease , 2009, Nature Reviews Immunology.

[25]  Elizabeth A. Kruse,et al.  Membrane-bound but not Secreted Fas Ligand Is Essential for Fas-Induced Apoptosis and Prevention of Autoimmunity and Cancer , 2009, Nature.

[26]  A. Hoffmann,et al.  The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes. , 2009, Molecular cell.

[27]  A. Strasser,et al.  NF-kappaB1 and c-Rel cooperate to promote the survival of TLR4-activated B cells by neutralizing Bim via distinct mechanisms. , 2008, Blood.

[28]  D. Hwang,et al.  Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. , 2008, Immunity.

[29]  Y. Tu,et al.  Tracking CD40 signaling during germinal center development. , 2004, Blood.

[30]  G. Leone,et al.  Cyclin E and Bcl-xL cooperatively induce cell cycle progression in c-Rel−/− B cells , 2003, Oncogene.

[31]  S. Smerdon,et al.  NF-κB1 p105 Negatively Regulates TPL-2 MEK Kinase Activity , 2003, Molecular and Cellular Biology.

[32]  M. Karin,et al.  IKKβ Is Required for Peripheral B Cell Survival and Proliferation1 , 2003, The Journal of Immunology.

[33]  A. Strasser,et al.  B cell growth is controlled by phosphatidylinosotol 3-kinase-dependent induction of Rel/NF-kappaB regulated c-myc transcription. , 2002, Molecular cell.

[34]  Hong-shan Wang,et al.  BAFF-induced NEMO-independent processing of NF-κB2 in maturing B cells , 2002, Nature Immunology.

[35]  K. Rajewsky,et al.  IκB Kinase Signaling Is Essential for Maintenance of Mature B Cells , 2002, The Journal of experimental medicine.

[36]  D. Baltimore,et al.  The combined absence of NF-κB1 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 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[37]  S. Ghosh,et al.  The Phosphorylation Status of Nuclear NF-ΚB Determines Its Association with CBP/p300 or HDAC-1 , 2002 .

[38]  J. Fox,et al.  Cutting Edge: Typhlocolitis in NF-κB-Deficient Mice1 , 2001, The Journal of Immunology.

[39]  G. Kollias,et al.  TNF-α Induction by LPS Is Regulated Posttranscriptionally via a Tpl2/ERK-Dependent Pathway , 2000, Cell.

[40]  Bruce H. Horwitz,et al.  Nuclear Factor κb Is Required for the Development of Marginal Zone B Lymphocytes , 2000, The Journal of experimental medicine.

[41]  M. Wiles,et al.  Interleukin 6 Influences Germinal Center Development and Antibody Production via a Contribution of C3 Complement Component , 1998, The Journal of experimental medicine.

[42]  A. Strasser,et al.  B Lymphocytes Differentially Use the Rel and Nuclear Factor κB1 (NF-κB1) Transcription Factors to Regulate Cell Cycle Progression and Apoptosis in Quiescent and Mitogen-activated Cells , 1998, The Journal of experimental medicine.

[43]  D. Baltimore,et al.  B cells from p50/NF-kappa B knockout mice have selective defects in proliferation, differentiation, germ-line CH transcription, and Ig class switching. , 1996, Journal of immunology.

[44]  David Baltimore,et al.  Targeted disruption of the p50 subunit of NF-κB leads to multifocal defects in immune responses , 1995, Cell.

[45]  S. Gerondakis,et al.  The subunit composition of NF-kappa B complexes changes during B-cell development. , 1994, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[46]  S. Akira,et al.  Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[47]  T. Libermann,et al.  Activation of interleukin-6 gene expression through the NF-kappa B transcription factor , 1990, Molecular and cellular biology.

[48]  Riccardo Dalla-Favera,et al.  Germinal centres: role in B-cell physiology and malignancy , 2008, Nature Reviews Immunology.

[49]  Steve,et al.  The Subunit Composition of NF-icB Complexes Changes during B-Cell Development ’ , 2005 .

[50]  Shao-Cong Sun,et al.  NF-kappaB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase. , 2003, Molecular cell.

[51]  Susan J Wilson,et al.  Nuclear Factor-(cid:2) B1 (p50) Limits the Inflammatory and Fibrogenic Responses to Chronic Injury , 2022 .