Requirement for TRAF3 in signaling by LMP1 but not CD40 in B lymphocytes

Ping Xie; Bruce S Hostager; Gail A Bishop

doi:10.1084/jem.20031255

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Requirement for TRAF3 in signaling by LMP1 but not CD40 in B lymphocytes

Journal article

Open access

Peer reviewed

Requirement for TRAF3 in signaling by LMP1 but not CD40 in B lymphocytes

Ping Xie, Bruce S Hostager and Gail A Bishop

The Journal of experimental medicine, Vol.199(5), pp.661-671

03/01/2004

DOI: 10.1084/jem.20031255

PMCID: PMC2213302

PMID: 14981114

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Abstract

CD40, a member of the tumor necrosis factor receptor family, and the Epstein-Barr virus-encoded oncoprotein latent membrane protein 1 (LMP1) share several tumor necrosis factor receptor-associated factor (TRAF) adaptor proteins for signaling. Among these, TRAF3 was the first identified to directly bind both receptors, yet its role remains a mystery. To address this, we generated B cell lines deficient in TRAF3 by homologous recombination. We found that CD40 signals were normal in the absence of TRAF3, with the exception of moderately enhanced c-Jun NH2-terminal kinase (JNK) activation and antibody secretion. In sharp contrast, LMP1 signaling was markedly defective in TRAF3-/- B cells. LMP1-induced activation of JNK and nuclear factor kappaB, up-regulation of CD23 and CD80, and antibody secretion were substantially affected by TRAF3 deficiency. Reconstitution of TRAF3 expression decreased CD40-induced JNK activation and antibody secretion, and fully restored LMP1 signaling. Although TRAF2 is widely believed to be important for LMP1 function, LMP1 signaling was intact in TRAF2-/- B cells. Our data reveal that CD40 and LMP1 unexpectedly use TRAF3 in different ways, and that TRAF3 is required for LMP1-mediated activation of B cells.

CD40 Antigens - physiology

Cell Line

Gene Targeting

Proteins - physiology

Signal Transduction

Herpesvirus 4, Human - physiology

B-Lymphocytes - physiology

Viral Matrix Proteins - physiology

TNF Receptor-Associated Factor 2

TNF Receptor-Associated Factor 3

Proteins - genetics

Animals

B-Lymphocytes - immunology

B-Lymphocytes - virology

Herpesvirus 4, Human - pathogenicity

Mice

Details

Title: Subtitle: Requirement for TRAF3 in signaling by LMP1 but not CD40 in B lymphocytes
Creators: Ping Xie - Department of Microbiology, University of Iowa, Iowa City 52242, USA
Bruce S Hostager
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.199(5), pp.661-671
Publisher: United States
DOI: 10.1084/jem.20031255
PMID: 14981114
PMCID: PMC2213302
ISSN: 0022-1007
eISSN: 1540-9538
Grant note: AI49993 / NIAID NIH HHS AI28847 / NIAID NIH HHS R01 AI028847 / NIAID NIH HHS R01 AI049993 / NIAID NIH HHS CA099997 / NCI NIH HHS R56 AI049993 / NIAID NIH HHS R01 CA099997 / NCI NIH HHS R56 AI028847 / NIAID NIH HHS
Language: English
Date published: 03/01/2004
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001206002771

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