B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice
In: Blood, Jg. 117 (2011), Heft 7, S. 2227-2236
Online
academicJournal
- print, 41 ref
Zugriff:
The ubiquitin-editing enzyme A20/TN-FAIP3 is essential for controlling signals inducing the activation of nuclear factor-KB 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-κB 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 progressive 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 class-switched, tissue-specific autoantibodies.
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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
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Autor/in / Beteiligte Person: | YUANYUAN, CHU ; VAHL, J. Christoph ; BEYAERT, Rudi ; AMANN, Kerstin ; VAN LOO, Geert ; SCHMIDT-SUPPRIAN, Marc ; KUMAR, Dilip ; HEGER, Klaus ; BERTOSSI, Arianna ; WOJTOWICZ, Edyta ; SOBERON, Valeria ; SCHENTEN, Dominik ; MACK, Brigitte ; REUTELSHÖFER, Miriam |
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Zeitschrift: | Blood, Jg. 117 (2011), Heft 7, S. 2227-2236 |
Veröffentlichung: | Washington, DC: Americain Society of Hematology, 2011 |
Medientyp: | academicJournal |
Umfang: | print, 41 ref |
ISSN: | 0006-4971 (print) |
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