The Ubiquitin Modifying Enzyme A20 Restricts B Cell Survival and Prevents Autoimmunity

Rita M. Tavares, Emre E. Turer, Chih L. Liu, Rommel Advincula, Patrizia Scapini, Lesley Rhee, Julio Barrera, Clifford A. Lowell, Paul J. Utz, Barbara A. Malynn, Averil Ma

Research output: Contribution to journalArticle

148 Scopus citations

Abstract

A20 is a ubiquitin modifying enzyme that restricts NF-κB 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-κB 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-κB-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.

Original languageEnglish (US)
Pages (from-to)181-191
Number of pages11
JournalImmunity
Volume33
Issue number2
DOIs
Publication statusPublished - Aug 1 2010

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Keywords

  • Cellimmuno
  • Molimmuno
  • Signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Tavares, R. M., Turer, E. E., Liu, C. L., Advincula, R., Scapini, P., Rhee, L., ... Ma, A. (2010). The Ubiquitin Modifying Enzyme A20 Restricts B Cell Survival and Prevents Autoimmunity. Immunity, 33(2), 181-191. https://doi.org/10.1016/j.immuni.2010.07.017