| First Author | Jin W | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 21 | Pages | 15884-93 |
| PubMed ID | 17392286 | Mgi Jnum | J:122705 |
| Mgi Id | MGI:3715085 | Doi | 10.1074/jbc.M609952200 |
| Citation | Jin W, et al. (2007) Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. J Biol Chem 282(21):15884-93 |
| abstractText | Deubiquitinating enzymes (DUB) form a family of cysteine proteases that digests ubiquitin chains and reverses the process of protein ubiquitination. Despite the identification of a large number of DUBs, their physiological functions remain poorly defined. Here we provide genetic evidence that CYLD, a recently identified DUB, plays a crucial role in regulating the peripheral development and activation of B cells. Disruption of the CYLD gene in mice results in B cell hyperplasia and lymphoid organ enlargement. The CYLD-deficient B cells display surface markers indicative of spontaneous activation and are hyperproliferative upon in vitro stimulation. When challenged with antigens, the CYLD(-/-) mice develop exacerbated lymphoid organ abnormalities and abnormal B cell responses. Although the loss of CYLD has only a minor effect on B cell development in bone marrow, this genetic deficiency disrupts the balance of peripheral B cell populations with a significant increase in marginal zone B cells. In keeping with these functional abnormalities, the CYLD(-/-) B cells exhibit constitutive activation of the transcription factor NF-kappaB due to spontaneous activation of IkappaB kinase beta and degradation of the NF-kappaB inhibitor IkappaBalpha. These findings demonstrate a critical role for CYLD in regulating the basal activity of NF-kappaB and maintaining the naive phenotype and proper activation of B cells. |
