期刊
IMMUNITY
卷 33, 期 2, 页码 181-191出版社
CELL PRESS
DOI: 10.1016/j.immuni.2010.07.017
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类别
资金
- National Institutes of Health
- Alliance for Lupus Research
- Fundacao para a Ciencia e Tecnologia
- UCSF-VAMC Pathology Core
- Cancer Center Pathology Core, UCSF Liver Center Immunology and Pathology Cores
- UCSF Transgenic and Targeted Mutagenesis Core Facility
- Rainin Foundation
A20 is a ubiquitin modifying enzyme that restricts NF-kappa B 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-kappa B 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-kappa B-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.
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