Enhanced Toll-like receptor (TLR) responses of TNFR-associated factor 3 (TRAF3)-deficient B lymphocytes

Ping Xie; Jayakumar Poovassery; Laura L Stunz; Sonja M Smith; Mark L Schultz; Lindsey E Carlin; Gail A Bishop

doi:10.1189/jlb.0111044

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Enhanced Toll-like receptor (TLR) responses of TNFR-associated factor 3 (TRAF3)-deficient B lymphocytes

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Enhanced Toll-like receptor (TLR) responses of TNFR-associated factor 3 (TRAF3)-deficient B lymphocytes

Ping Xie, Jayakumar Poovassery, Laura L Stunz, Sonja M Smith, Mark L Schultz, Lindsey E Carlin and Gail A Bishop

Journal of leukocyte biology, Vol.90(6), pp.1149-1157

12/2011

DOI: 10.1189/jlb.0111044

PMCID: PMC3236554

PMID: 21971520

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Abstract

TRAF3 decreases B-cell early signals and downstream functions in response to Toll-like receptors. The key role of TRAF6 in TLR signaling pathways is well known. More recent evidence has implicated TRAF3 as another TRAF family member important to certain TLR responses of myeloid cells. Previous studies demonstrate that TRAF3 functions are highly context-dependent, displaying receptor and cell-type specificity. We thus examined the TLR responses of TRAF3 −/− mouse B lymphocytes to test the hypothesis that TRAF3 plays distinct roles in such responses, depending on cell type. TRAF3 −/− DC are known to have a defect in type 1 IFN production and here, showed diminished production of TNF and IL-10 and unaltered IL-6. In marked contrast, TRAF3 −/− B cells made elevated amounts of TNF and IL-6 protein, as well as IL-10 and IP-10 mRNA, in response to TLR ligands. Also, in contrast to TRAF3 −/− DC, the type 1 IFN pathway was elevated in TRAF3 −/− B cells. Increased early responses of TRAF3 −/− B cells to TLR signals were independent of cell survival or proliferation but associated with elevated canonical NF-κB activation. Additionally, TRAF3 −/− B cells displayed enhanced TLR-mediated expression of AID and Ig isotype switching. Thus, TRAF3 plays varied and cell type-specific, biological roles in TLR responses.

lymphocyte activation

Receptors, Signal Transduction, & Genes

innate immunity

signal transduction

Details

Title: Subtitle: Enhanced Toll-like receptor (TLR) responses of TNFR-associated factor 3 (TRAF3)-deficient B lymphocytes
Creators: Ping Xie - Department of Microbiology
Jayakumar Poovassery - Department of Microbiology
Laura L Stunz - Department of Microbiology
Sonja M Smith - Department of Microbiology
Mark L Schultz - Molecular and Cellular Biology and
Lindsey E Carlin - Immunology, The University of Iowa, and
Gail A Bishop - Iowa City Veterans Affairs Medical Center, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Journal of leukocyte biology, Vol.90(6), pp.1149-1157
DOI: 10.1189/jlb.0111044
PMID: 21971520
PMCID: PMC3236554
NLM abbreviation: J Leukoc Biol
ISSN: 0741-5400
eISSN: 1938-3673
Publisher: Society for Leukocyte Biology; Bethesda, MD, USA
Grant note: R01 AI28847 / National Institutes of Health
Language: English
Date published: 12/2011
Academic Unit: Microbiology and Immunology; President; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biochemistry and Molecular Biology
Record Identifier: 9984001201402771

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