6533b824fe1ef96bd128146e
RESEARCH PRODUCT
A20 deficiency in B cells enhances B-cell proliferation and results in the development of autoantibodies.
Ari WaismanPetra Adams-quackNguyen Thi XuanDirk SchlüterDominika LukasSonja ReissigNadine HövelmeyerAlexei Nikolaevsubject
ImmunologyB-Lymphocyte SubsetsInflammationBiologymedicine.disease_causeLymphocyte ActivationGermlineAutoimmunityMiceimmune system diseaseshemic and lymphatic diseasesmedicineImmunology and AllergyAnimalsHumansTumor Necrosis Factor alpha-Induced Protein 3AutoantibodiesCell ProliferationMice KnockoutB-LymphocytesCell growthAutoantibodyIntracellular Signaling Peptides and ProteinsNF-kappa BMarginal zoneGerminal CenterMolecular biologyPhenotypeCell biologyCysteine EndopeptidasesModels Animalbiology.proteinmedicine.symptomAntibodySignal Transductiondescription
A20/TNFAIP3 is an ubiquitin-editing enzyme, important for the regulation of the NF-κB pathway. Mutations in the TNFAIP3 gene have been linked to different human autoimmune disorders. In human B-cell lymphomas, the inactivation of A20 results in constitutive NF-κB activation. Recent studies demonstrate that in mice the germline inactivation of A20 leads to early lethality, due to inflammation in multiple organs of the body. In this report, we describe a new mouse strain allowing for the tissue-specific deletion of A20. We show that B-cell-specific deletion of A20 results in a dramatic reduction in marginal zone B cells. Furthermore, A20-deficient B cells display a hyperactive phenotype represented by enhanced proliferation upon activation. Finally, these mice develop higher levels of serum immunoglobulins, resulting in an excessive production of self-reactive autoantibodies.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-02-10 | European journal of immunology |