| First Author | Tavares RM | Year | 2010 |
| Journal | Immunity | Volume | 33 |
| Issue | 2 | Pages | 181-91 |
| PubMed ID | 20705491 | Mgi Jnum | J:163917 |
| Mgi Id | MGI:4830189 | Doi | 10.1016/j.immuni.2010.07.017 |
| Citation | Tavares RM, et al. (2010) The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity. Immunity 33(2):181-91 |
| abstractText | 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. |
