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

Kövesdi, Dorottya and Angyal, A. and Huber, K. and Szili, Dániel and Sármay, Gabriella (2013) T-bet is a new synergistic meeting point for the BCR and TLR9 signaling cascades. EUROPEAN JOURNAL OF IMMUNOLOGY, 44 (3). pp. 887-893. ISSN 0014-2980

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The importance of the BCR and TLR9 in autoimmunity and in the production of autoantibodies is well established but the underlying molecular mechanism still needs to be determined. Here we aim to characterize the BCR-TLR9 crosstalk 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 crosstalk 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 co-stimulation 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 CIA (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.

Item Type: Article
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: MTMT SWORD
Date Deposited: 15 Jan 2015 10:58
Last Modified: 15 Jan 2015 10:58

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