Journal article
Antigen Receptor Signals Rescue B Cells From TLR Tolerance
The Journal of immunology (1950), Vol.183(5), pp.2974-2983
09/01/2009
DOI: 10.4049/jimmunol.0900495
PMCID: PMC2789010
PMID: 19648281
Abstract
Interactions between innate and adaptive immune receptors are critical for an optimal immune response, but the role played by antigen receptors in modulating innate receptor functions is less clear. TLRs are a family of pattern recognition receptors that play crucial roles in detecting microbial pathogens and subsequent development of immune responses. However, chronic stimulation through TLRs render immune cells hyporesponsive to subsequent stimulation with TLR ligands; a phenomenon known as TLR tolerance, well characterized in myeloid cells. However, it has not been studied in detail in B lymphocytes. In addition to the BCR, B cells express almost all known TLRs and respond robustly to many TLR ligands. Thus, B cells may receive signals through both TLRs and BCR during an infection and may respond differently to TLR stimulation than myeloid cells. We tested this possibility by stimulating repeatedly through either TLR alone or through both TLR and BCR. Prestimulation through TLR7 resulted in reduced B cell proliferation, cytokine production and IgM secretion upon subsequent TLR7 restimulation. The hyporesponsiveness to TLR7 restimulation was associated with reduced NF-κB and MAP kinase activation and defective c-Jun phosphorylation. However, simultaneous BCR signaling prevented or reversed TLR7 tolerance in both mouse and human B cells. Importantly, BCR signaling also rescued B cells from TLR7-mediated TLR9 tolerance. Additionally, the reversal of TLR7-mediated JNK activation was dependent on phosphatidylinositol 3-kinase activation. Together these results present a novel mechanism to prevent and reverse TLR tolerance in B cells.
Details
- Title: Subtitle
- Antigen Receptor Signals Rescue B Cells From TLR Tolerance
- Creators
- Jayakumar S Poovassery - Iowa City Veterans’ Affairs Medical center, Iowa City, IA 52242Tony J Vanden Bush - Iowa City Veterans’ Affairs Medical center, Iowa City, IA 52242Gail A Bishop - Iowa City Veterans’ Affairs Medical center, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.183(5), pp.2974-2983
- DOI
- 10.4049/jimmunol.0900495
- PMID
- 19648281
- PMCID
- PMC2789010
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 09/01/2009
- Academic Unit
- Microbiology and Immunology; President
- Record Identifier
- 9984001231202771
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