In:
Journal of Experimental Medicine, Rockefeller University Press, Vol. 207, No. 12 ( 2010-11-22), p. 2569-2579
Kurzfassung:
The cytokine B cell activating factor (BAFF) and its receptor, BAFF receptor (BAFF-R), modulate signaling cascades critical for B cell development and survival. We identified a novel mutation in TNFRSF13C, the gene encoding human BAFF-R, that is present in both tumor and germline tissue from a subset of patients with non-Hodgkin lymphoma. This mutation encodes a His159Tyr substitution in the cytoplasmic tail of BAFF-R adjacent to the TRAF3 binding motif. Signaling through this mutant BAFF-R results in increased NF-κB1 and NF-κB2 activity and increased immunoglobulin production compared with the wild-type (WT) BAFF-R. This correlates with increased TRAF2, TRAF3, and TRAF6 recruitment to His159Tyr BAFF-R. In addition, we document a requirement for TRAF6 in WT BAFF-R signaling. Together, these data identify a novel lymphoma-associated mutation in human BAFF-R that results in NF-κB activation and reveals TRAF6 as a necessary component of normal BAFF-R signaling.
Materialart:
Online-Ressource
ISSN:
1540-9538
,
0022-1007
DOI:
10.1084/jem.20100857
Sprache:
Englisch
Verlag:
Rockefeller University Press
Publikationsdatum:
2010
ZDB Id:
1477240-1
