A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling

Joanne M. Hildebrand, Zhenghua Luo, Michelle K. Manske, Tammy Price-Troska, Steven C. Ziesmer, Wai Lin, Bruce S. Hostager, Susan L Slager, Thomas Elmer Witzig, Stephen Maxted Ansell, James R Cerhan, Gail A. Bishop, Anne J Novak

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2569-2579
Number of pages11
JournalJournal of Experimental Medicine
Volume207
Issue number12
DOIs
StatePublished - Nov 22 2010

Fingerprint

B-Cell Activation Factor Receptor
Non-Hodgkin's Lymphoma
Mutation
TNF Receptor-Associated Factor 6
TNF Receptor-Associated Factor 3
TNF Receptor-Associated Factor 2
B-Cell Activating Factor
Tail
Immunoglobulins
Lymphoma
Cell Survival
B-Lymphocytes
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling. / Hildebrand, Joanne M.; Luo, Zhenghua; Manske, Michelle K.; Price-Troska, Tammy; Ziesmer, Steven C.; Lin, Wai; Hostager, Bruce S.; Slager, Susan L; Witzig, Thomas Elmer; Ansell, Stephen Maxted; Cerhan, James R; Bishop, Gail A.; Novak, Anne J.

In: Journal of Experimental Medicine, Vol. 207, No. 12, 22.11.2010, p. 2569-2579.

Research output: Contribution to journalArticle

Hildebrand, Joanne M. ; Luo, Zhenghua ; Manske, Michelle K. ; Price-Troska, Tammy ; Ziesmer, Steven C. ; Lin, Wai ; Hostager, Bruce S. ; Slager, Susan L ; Witzig, Thomas Elmer ; Ansell, Stephen Maxted ; Cerhan, James R ; Bishop, Gail A. ; Novak, Anne J. / A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling. In: Journal of Experimental Medicine. 2010 ; Vol. 207, No. 12. pp. 2569-2579.
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