Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 207, Issue 12, Pages 2569-2579Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20100857
Keywords
-
Categories
Funding
- Australian NHMRC [541951]
- National Institutes of Health [R01AI49993, P50CA097274, R01CA92153]
- Dept. of Veterans Affairs
- Lymphoma Research Foundation
- Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development
Ask authors/readers for more resources
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-kappa B1 and NF-kappa B2 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-kappa B activation and reveals TRAF6 as a necessary component of normal BAFF-R signaling.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available