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

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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--B 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.

Original languageEnglish (US)
Pages (from-to)1149-1157
Number of pages9
JournalJournal of Leukocyte Biology
Volume90
Issue number6
DOIs
StatePublished - Dec 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Keywords

  • Innate immunity
  • Lymphocyte activation
  • Signal transduction

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