A20 deficiency in B cells enhances B-cell proliferation and results in the development of autoantibodies

Eur J Immunol. 2011 Mar;41(3):595-601. doi: 10.1002/eji.201041313. Epub 2011 Feb 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis*
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Proliferation
  • Cysteine Endopeptidases / deficiency
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / immunology
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Humans
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Models, Animal
  • NF-kappa B / immunology
  • Signal Transduction
  • Tumor Necrosis Factor alpha-Induced Protein 3


  • Autoantibodies
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Cysteine Endopeptidases
  • Tnfaip3 protein, mouse