Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs

Ping Xie; Laura L. Stunz; Karen D. Larison; Baoli Yang; Gail A. Bishop

doi:10.1016/j.immuni.2007.07.012

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Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs

Journal article

Open access

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Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs

Ping Xie, Laura L. Stunz, Karen D. Larison, Baoli Yang and Gail A. Bishop

Immunity, Vol.27(2), pp.253-267

08/01/2007

DOI: 10.1016/j.immuni.2007.07.012

PMCID: PMC2084086

PMID: 17723217

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Abstract

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an adaptor protein that directly binds to a number of receptors of the tumor necrosis factor receptor (TNF-R) superfamily. Despite in vitro evidence that TRAF3 plays diverse roles in different cell types, little is known about the in vivo functions of TRAF3. To address this gap in knowledge and to circumvent the early lethal effect of TRAF3 null mutations, we generated conditional TRAF3-deficient mice. B-cell-specific Traf3(-/-) mice displayed severe peripheral B cell hyperplasia, which culminated in hyperimmunoglobulinemia and increased T-independent antibody responses, splenomegaly and lymphadenopathy. Resting splenic B cells from these mice exhibited remarkably prolonged survival ex vivo independent of B cell activating factor and showed increased amounts of active nuclear factor-kappaB2 but decreased amounts of nuclear protein kinase Cdelta. Furthermore, these mice developed autoimmune manifestations as they aged. These findings indicate that TRAF3 is a critical regulator of peripheral B cell homeostasis and may be implicated in the regulation of peripheral self-tolerance induction.

Tumor Immunology

Obstetrics and Gynecology

Details

Title: Subtitle: Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs
Creators: Ping Xie
Laura L. Stunz
Karen D. Larison
Baoli Yang - University of Iowa
Gail A. Bishop
Resource Type: Journal article
Publication Details: Immunity, Vol.27(2), pp.253-267
DOI: 10.1016/j.immuni.2007.07.012
PMID: 17723217
PMCID: PMC2084086
NLM abbreviation: Immunity
ISSN: 1074-7613
Language: English
Date published: 08/01/2007
Academic Unit: Microbiology and Immunology; President; Obstetrics and Gynecology
Record Identifier: 9983557421602771

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