T-bet is a new synergistic meeting point for the BCR and TLR9 signaling cascades

Dorottya Kövesdi, Adrienn Angyal, Krisztina Huber, Dániel Szili, Gabriella Sármay

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The importance of the BCR and TLR9 in autoimmunity and in the production of auto-antibodies is well established but the underlying molecular mechanism still needs to be determined. Here, we aim to characterize the BCR-TLR9 cross-talk by its effect on T-bet, as T-bet is activated and regulated by both receptors and has an important role in class-switching to pathological IgG2a in mice. Using primary mouse B cells, we demonstrate that T-bet expression is synergistically elevated by the cross-talk between the BCR and TLR9. To test the effect of this synergy on IgG2a-switching, the levels of switched B cells were checked by functional tests. We found that BCR costimulation had no additional effect on TLR9-induced IgG2a expression, however the expression of Rad51 was synergistically increased. To check the biological significance of the synergy, we compared T-bet expression in B cells from healthy and collagen-induced arthritis mice but no differences were found. Taken together, we demonstrate here that signaling cascades driven by the BCR and TLR9 have a newly identified meeting point at T-bet. The two cascades act synergistically on T-bet; however additional signals may be needed to induce prolonged functional responses such as class-switch recombination.

Original languageEnglish
Pages (from-to)887-893
Number of pages7
JournalEuropean journal of immunology
Volume44
Issue number3
DOIs
Publication statusPublished - Mar 2014

Keywords

  • BCR
  • Signaling
  • Synergy
  • T-bet
  • TLR9

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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