T ‐bet is a new synergistic meeting point for the BCR and TLR 9 signaling cascades

• Published in: European journal of immunology 2014-03, Vol.44 (3), p.887-893
• Main Authors: Kövesdi, Dorottya, Angyal, Adrienn, Huber, Krisztina, Szili, Dániel, Sármay, Gabriella
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201343841

The importance of the BCR and TLR 9 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 ‐ TLR 9 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 I g G 2a in mice. Using primary mouse B cells, we demonstrate that T ‐bet expression is synergistically elevated by the cross‐talk between the BCR and TLR 9. To test the effect of this synergy on I g G 2a‐switching, the levels of switched B cells were checked by functional tests. We found that BCR costimulation had no additional effect on TLR 9‐induced I g G 2a expression, however the expression of R ad51 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 TLR 9 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.