Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Leukoc Biol. 2010 Oct;88(4):779-89. doi: 10.1189/jlb.0410237. Epub 2010 Jul 14.

TLR-mediated B cell activation results in ectopic CLIP expression that promotes B cell-dependent inflammation.

Author information

  • 1CU Institute for Bioenergetics and Immunology, University of Colorado at Colorado Springs, Colorado, USA. newellrogers@medicine.tamhsc.edu

Erratum in

  • J Leukoc Biol. 2010 Dec;88(6):1279.

Abstract

Infectious pathogens produce compounds called Toll ligands that activate TLRs on lymphocytes. Acute activation triggered by certain TLRs appears to "jump start" the innate immune response, characterized by the release of inflammatory cytokines and cellular expansion. In some individuals, there is a failure to control acute inflammation, resulting in postinfectious, chronic inflammation. Susceptibility to chronic inflammation is strongly associated with an individual's MHC genes. Recent clinical trials for several autoimmune diseases characterized by chronic inflammation suggest that B lymphocyte depletion therapies dampen chronic immune activation. However, currently, there is no known mechanism that accounts for the correlation among TLR activation, MHC genetics, and a pathological role for B-lymphocytes. Our hypothesis is that TLR-activated B cells (B cells that have been polyclonally activated in the absence of antigen-specific signals) are not controlled properly by T cell-dependent B cell death, thereby causing B cell-dependent chronic inflammation. Here, we show that treatment with Toll ligands results in polyclonal B cell activation accompanied by ectopic expression of CLIP. Furthermore, by adoptively transferring purified CLIP+ B cells in syngeneic animals, we find that CLIP+ B cells induce production of TNF-α by host T cells. Finally, we demonstrate that CLIP-targeted peptide competition results in the death of polyclonally activated CLIP+ B cells.

PMID:
20631258
[PubMed - indexed for MEDLINE]
PMCID:
PMC3218675
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk