|
|
Blood, 7 May 2009, Vol. 113, No. 19, pp. 4627-4636.
Prepublished online as a Blood First Edition Paper on March 3, 2009; DOI 10.1182/blood-2008-10-183467.
 Previous Article | Table of Contents | Next Article 
LYMPHOID NEOPLASIA
BAFF-R promotes cell proliferation and survival through interaction with IKKβ and NF- B/c-Rel in the nucleus of normal and neoplastic B-lymphoid cells
Lingchen Fu1,
Yen-Chiu Lin-Lee1,
Lan V. Pham1,
Archito T. Tamayo1,
Linda C. Yoshimura1, and
Richard J. Ford1
1 Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston
BLyS and its major receptor BAFF-R have been shown to be critical for development and homeostasis of normal B lymphocytes, and for cell growth and survival of neoplastic B lymphocytes, but the biologic mechanisms of this ligand/receptor-derived intracellular signaling pathway(s) have not been completely defined. We have discovered that the BAFF-R protein was present in the cell nucleus, in addition to its integral presence in the plasma membrane and cytoplasm, in both normal and neoplastic B cells. BAFF-R interacted with histone H3 and IKKβ in the cell nucleus, enhancing histone H3 phosphorylation through IKKβ. Nuclear BAFF-R was also associated with NF- B/c-Rel and bound to NF-B targeted promoters including BLyS, CD154, Bcl-xL, IL-8, and Bfl-1/A1, promoting the transcription of these genes. These observations suggested that in addition to activating NF-B pathways in the plasma membrane, BAFF-R also promotes normal B-cell and B-cell non-Hodgkin lymphoma (NHL-B) survival and proliferation by functioning as a transcriptional regulator through a chromatin remodeling mechanism(s) and NF-B association. Our studies provide an expanded conceptual view of the BAFF-R signaling, which should contribute a better understanding of the physiologic mechanisms involved in normal B-cell survival and growth, as well as in the pathophysiology of aggressive B-cell malignancies and autoimmune diseases.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
W. N. Khan
B Cell Receptor and BAFF Receptor Signaling Regulation of B Cell Homeostasis
J. Immunol.,
September 15, 2009;
183(6):
3561 - 3567.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
