SCIENCE@home

Deubiquitinating Enzyme CYLD Regulates the Peripheral Development and Naive Phenotype Maintenance of B Cells*♦

W. Jin,William R Reiley,Andrew J. Lee,Ato O. Wright,Xuefeng Wu,Minying Zhang,Shao-Cong Sun

Published 2007 in Journal of Biological Chemistry

ABSTRACT

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-κB due to spontaneous activation of IκB kinase β and degradation of the NF-κB inhibitor IκBα. These findings demonstrate a critical role for CYLD in regulating the basal activity of NF-κB and maintaining the naive phenotype and proper activation of B cells.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-56 of 56 references · Page 1 of 1

CITED BY

Showing 1-79 of 79 citing papers · Page 1 of 1