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The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity.

Immunity | Aug 27, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20705491

A20 is a ubiquitin modifying enzyme that restricts NF-kappaB signals and protects cells against tumor necrosis factor (TNF)-induced programmed cell death. Given recent data linking A20 (TNFAIP3) with human B cell lymphomas and systemic lupus erythematosus (SLE), we have generated mice bearing a floxed allele of Tnfaip3 to interrogate A20's roles in regulating B cell functions. A20-deficient B cells are hyperresponsive to multiple stimuli and display exaggerated NF-kappaB responses to CD40-induced signals. Mice expressing absent or hypomorphic amounts of A20 in B cells possess elevated numbers of germinal center B cells, autoantibodies, and glomerular immunoglobulin deposits. A20-deficient B cells are resistant to Fas-mediated cell death, probably due to increased expression of NF-kappaB-dependent antiapoptotic proteins such as Bcl-x. These findings show that A20 can restrict B cell survival, whereas A20 protects other cells from TNF-induced cell death. Our studies demonstrate how reduced A20 expression predisposes to autoimmunity.

Pubmed ID: 20705491 RIS Download

Mesh terms: Animals | Antigens, CD40 | Autoimmunity | B-Lymphocytes | Cell Lineage | Cell Survival | Cysteine Endopeptidases | Homeostasis | Intracellular Signaling Peptides and Proteins | Mice | Mice, Inbred C57BL | Mice, Knockout | NF-kappa B | Signal Transduction

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Associated grants

  • Agency: NIAID NIH HHS, Id: P01 AI078869
  • Agency: NIAID NIH HHS, Id: P01 AI078869-010002
  • Agency: NIAID NIH HHS, Id: R01 AI068150
  • Agency: NIDDK NIH HHS, Id: R01 DK071939
  • Agency: NIDDK NIH HHS, Id: R01 DK071939-06

Mouse Genome Informatics (Data, Gene Annotation)

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