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Researchers Discover a New Molecular Mechanism of T-follicular helper differentiation and antibody Production
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In a featured study published online in PNAS on August 7, 2018, a group led by Prof. SUN Bing from Shanghai Institute of Biochemistry and Cell Biology, CAS, in collaboration with Prof. WANG Haikun from Institute Pasteur of Shanghai, CAS reported a new molecular mechanism of follicular helper T cell differentiation.
T-follicular helper (TFH) cells are a subset of CD4+helper T cells that help germinal center (GC) B-cell differentiation and high-affinity antibody production following the antigen stimulation. TFH cell differentiation is generally considered as a multiple step. Like other subsets of helper T cells, the cytokine niche is essential for TFH differentiation. Interleukin IL-6 and IL-21 play central roles in TFH cell differentiation in mice. In contrast, IL-2 is a potent negative regulator of TFH differentiation.
In this work, scientists found that ECM1 was expressed at high levels in TFH cells; ECM1 deficiency impaired TFH germinal center formation, and antigen-specific antibody production. Treatment with recombinant ECM1 protein in wild-type mice enhanced TFH development and GC B-cell responses in vivo. Importantly, recombinant ECM1 protein administration enhanced TFH differentiation and neutralizing antibody production, which might be helpful for inducing protective immune responses against PR8 influenza virus. Further study found that ECM1 inhibited IL-2 –STAT5 signaling pathway, down-regulated Blimp-1 expression, and enhanced Bcl6 expression in TFH cells. Thus, the data demonstrated that ECM1 was a positive regulator of TFH differentiation and antibody production.
This study was supported by the grants from Chinese Academy of Sciences, the Ministry of Science and Technology of China, and the National Natural Science Foundation of China.
SUN Bing, Ph.D.
Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences,CAS , Shanghai, China
Email: bsun@sibs.ac.cn
Tel: +86-21-54921376


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