Journal article
A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling
The Journal of experimental medicine, Vol.207(12), pp.2569-2579
11/22/2010
DOI: 10.1084/jem.20100857
PMCID: PMC2989778
PMID: 21041452
Abstract
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.
Details
- Title: Subtitle
- A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling
- Creators
- Joanne M Hildebrand - Department of Microbiology, Department of Internal Medicine, and the Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242Zhenghua Luo - Department of Microbiology, Department of Internal Medicine, and the Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242Michelle K Manske - Department of Microbiology, Department of Internal Medicine, and the Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242Tammy Price-Troska - Department of Microbiology, Department of Internal Medicine, and the Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242Steven C Ziesmer - Department of Microbiology, Department of Internal Medicine, and the Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242Wai Lin - Department of Microbiology, Department of Internal Medicine, and the Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242Bruce S Hostager - Department of Microbiology, Department of Internal Medicine, and the Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242Susan L Slager - Division of Hematology, Division of Biomedical Statistics and Informatics, and Division of Epidemiology, Mayo Clinic, Rochester, MN 55905Thomas E Witzig - Division of Hematology, Division of Biomedical Statistics and Informatics, and Division of Epidemiology, Mayo Clinic, Rochester, MN 55905Stephen M Ansell - Division of Hematology, Division of Biomedical Statistics and Informatics, and Division of Epidemiology, Mayo Clinic, Rochester, MN 55905James R Cerhan - Division of Hematology, Division of Biomedical Statistics and Informatics, and Division of Epidemiology, Mayo Clinic, Rochester, MN 55905Gail A Bishop - Department of Microbiology, Department of Internal Medicine, and the Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242, Department of Microbiology, Department of Internal Medicine, and the Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242, Department of Microbiology, Department of Internal Medicine, and the Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242Anne J Novak - Division of Hematology, Division of Biomedical Statistics and Informatics, and Division of Epidemiology, Mayo Clinic, Rochester, MN 55905
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.207(12), pp.2569-2579
- DOI
- 10.1084/jem.20100857
- PMID
- 21041452
- PMCID
- PMC2989778
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 11/22/2010
- Academic Unit
- Microbiology and Immunology; President; Epidemiology
- Record Identifier
- 9984001217002771
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