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

نویسندگان

  • Weifeng Xu
  • J Jillian Zhang
چکیده

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-gamma 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-gamma 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-gamma. 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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance.

IgG2a is known to be the most efficient antibody isotype for viral clearance. Here, we demonstrate a unique pathway of B-cell activation, leading to IgG2a production, and involving synergistic stimulation via B-cell antigen receptors, toll-like receptor 7 (TLR7), and IFNγ receptors on B cells. This synergistic stimulation leads to induction of T-box transcription factor T-bet expression in B ce...

متن کامل

Induction of IgG2a class switching in B cells by IL-27.

IL-27 is a novel IL-12 family member that plays a role in the early regulation of Th1 initiation. However, its role in B cells remains unexplored. We here show a role for IL-27 in the induction of T-bet expression and regulation of Ig class switching in B cells. Expression of WSX-1, one subunit of IL-27R, was detected at the mRNA level in primary mouse spleen B cells, and stimulation of these B...

متن کامل

B and T Lymphocyte Attenuator is a Target of miR-155 during Naive CD4+ T Cell Activation

Background: MicroRNA-155 (miR-155) is upregulated during T cell activation, but the exact mechanisms by which it influences CD4+ T cell activation remain unclear. Objective: To examine whether the B and T lymphocyte attenuator (BTLA) is a target of miR-155 during naïve CD4+ T cell activation. Methods: Firefly luciferase reporter plasmids pEZX-MT01-wild-type-BTLA and pEZX-MT01-mutant-BTLA were ...

متن کامل

An indispensable role for STAT1 in IL-27-induced T-bet expression but not proliferation of naive CD4+ T cells.

IL-27 is a novel IL-12 family member that plays a role in the early regulation of Th1 initiation, induces proliferation of naive CD4+ T cells, and synergizes with IL-12 in IFN-gamma production. It has been recently reported that IL-27 induces T-bet and IL-12Rbeta2 expression through JAK1/STAT1 activation. In the present study, we further investigated the JAK/STAT signaling molecules activated b...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of immunology

دوره 175 11  شماره 

صفحات  -

تاریخ انتشار 2005