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B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice

(2011) BLOOD. 117(7). p.2227-2236
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Abstract
The ubiquitin-editing enzyme A20/TNFAIP3 is essential for controlling signals inducing the activation of nuclear factor- kappa B transcription factors. Polymorphisms and mutations in the TNFAIP3 gene are linked to various human autoimmune conditions, and inactivation of A20 is a frequent event in human B-cell lymphomas characterized by constitutive nuclear factor-kappa B activity. Through B cell-specific ablation in the mouse, we show here that A20 is required for the normal differentiation of the marginal zone B and B1 cell subsets. However, loss of A20 in B cells lowers their activation threshold and enhances proliferation and survival in a gene-dose-dependent fashion. Through the expression of proinflammatory cytokines, most notably interleukin- 6, A20-deficient B cells trigger a pro-gressive inflammatory reaction in naive mice characterized by the expansion of myeloid cells, effector-type T cells, and regulatory T cells. This culminates in old mice in an autoimmune syndrome characterized by splenomegaly, plasma cell hyperplasia, and the presence of classswitched, tissue-specific autoantibodies.
Keywords
GERMINAL-CENTERS, RHEUMATOID-ARTHRITIS, SYSTEMIC-LUPUS-ERYTHEMATOSUS, NF-KAPPA-B, T-CELLS, A20, IL-6, LYMPHOMA, DISEASE, GENE

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Citation

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Chicago
Chu, Yuanyuan, J Christoph Vahl, Dilip Kumar, Klaus Heger, Arianna Bertossi, Edyta Wojtowicz, Valeria Soberon, et al. 2011. “B Cells Lacking the Tumor Suppressor TNFAIP3/A20 Display Impaired Differentiation and Hyperactivation and Cause Inflammation and Autoimmunity in Aged Mice.” Blood 117 (7): 2227–2236.
APA
Chu, Y., Vahl, J. C., Kumar, D., Heger, K., Bertossi, A., Wojtowicz, E., Soberon, V., et al. (2011). B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice. BLOOD, 117(7), 2227–2236.
Vancouver
1.
Chu Y, Vahl JC, Kumar D, Heger K, Bertossi A, Wojtowicz E, et al. B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice. BLOOD. 2011;117(7):2227–36.
MLA
Chu, Yuanyuan, J Christoph Vahl, Dilip Kumar, et al. “B Cells Lacking the Tumor Suppressor TNFAIP3/A20 Display Impaired Differentiation and Hyperactivation and Cause Inflammation and Autoimmunity in Aged Mice.” BLOOD 117.7 (2011): 2227–2236. Print.
@article{1187357,
  abstract     = {The ubiquitin-editing enzyme A20/TNFAIP3 is essential for controlling signals inducing the activation of nuclear factor- kappa B transcription factors. Polymorphisms and mutations in the TNFAIP3 gene are linked to various human autoimmune conditions, and inactivation of A20 is a frequent event in human B-cell lymphomas characterized by constitutive nuclear factor-kappa B activity. Through B cell-specific ablation in the mouse, we show here that A20 is required for the normal differentiation of the marginal zone B and B1 cell subsets. However, loss of A20 in B cells lowers their activation threshold and enhances proliferation and survival in a gene-dose-dependent fashion. Through the expression of proinflammatory cytokines, most notably interleukin- 6, A20-deficient B cells trigger a pro-gressive inflammatory reaction in naive mice characterized by the expansion of myeloid cells, effector-type T cells, and regulatory T cells. This culminates in old mice in an autoimmune syndrome characterized by splenomegaly, plasma cell hyperplasia, and the presence of classswitched, tissue-specific autoantibodies.},
  author       = {Chu, Yuanyuan and Vahl, J Christoph and Kumar, Dilip and Heger, Klaus and Bertossi, Arianna and Wojtowicz, Edyta and Soberon, Valeria and Schenten, Dominik and Mack, Brigitte and Reutelshofer, Miriam and Beyaert, Rudi and Amann, Kerstin and van Loo, Geert and Schmidt-Supprian, Marc},
  issn         = {0006-4971},
  journal      = {BLOOD},
  keyword      = {GERMINAL-CENTERS,RHEUMATOID-ARTHRITIS,SYSTEMIC-LUPUS-ERYTHEMATOSUS,NF-KAPPA-B,T-CELLS,A20,IL-6,LYMPHOMA,DISEASE,GENE},
  language     = {eng},
  number       = {7},
  pages        = {2227--2236},
  title        = {B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice},
  url          = {http://dx.doi.org/10.1182/blood-2010-09-306019},
  volume       = {117},
  year         = {2011},
}

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