Stat1-dependent synergistic activation of T-bet for IgG2a production during early stage of B cell activation

W Xu, JJ Zhang - The Journal of Immunology, 2005 - journals.aai.org
W Xu, JJ Zhang
The Journal of Immunology, 2005journals.aai.org
During the adaptive phase of an immune response, naive B cells receive multiple signals to
become activated. Among them are the engagement of the B cell Ag receptor and
stimulation by cytokines. Specifically for an anti-microbial response, the recognition of viral
or bacterial Ags by the BCR and the stimulation of IFN-γ result in the predominant production
of IgG2a. The T-bet protein has been shown to be required for class switching to IgG2a. In
this report we further investigated the regulation of T-bet gene expression during the early …
Abstract
During the adaptive phase of an immune response, naive B cells receive multiple signals to become activated. Among them are the engagement of the B cell Ag receptor and stimulation by cytokines. Specifically for an anti-microbial response, the recognition of viral or bacterial Ags by the BCR and the stimulation of IFN-γ result in the predominant production of IgG2a. The T-bet protein has been shown to be required for class switching to IgG2a. In this report we further investigated the regulation of T-bet gene expression during the early stage of B cell activation. We show that there is a striking synergistic activation of T-bet in primary B cells when both the BCR and IFN-γ signaling pathways are activated. The synergistic activation of T-bet correlates with a 100% increase in the number of B cells that produce IgG2a. This transcription synergy on T-bet is transient in the first 24 h of B cell activation. Furthermore, we demonstrate that the synergistic activation of T-bet is dependent on Stat1 and that Stat1 is required for the IgG2a germline transcription and the production of IgG2a in response to the simultaneous signaling of BCR and IFN-γ. Finally, we show that Stat1 directly regulates the expression of T-bet by binding to the T-bet promoter. These results reveal the mechanism of regulation of T-bet expression and uncover a novel physiological function of Stat1 for B cell activation.
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