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

Autor: Kövesdi, Dorottya, Angyal, Adrienn, Huber, Krisztina, Szili, Dániel, Sármay, Gabriella
Zdroj: European Journal of Immunology; Mar2014, Vol. 44 Issue 3, p887-893, 7p
Abstrakt: 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 Ig G2a 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 Ig G2a-switching, the levels of switched B cells were checked by functional tests. We found that BCR costimulation had no additional effect on TLR9-induced Ig G2a 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index