Prof. Baidong Hou‘s group revealed an unexpected pathway by which naïve CD4+ T cells are activated


Prof. Baidong Hou‘s group published a research article in Immunity about an unexpected pathway by which naïve CD4+ T cells are activated (Sheng Hong, Zhimin Zhang, Hongtao Liu, Meijie Tian, Xiping Zhu, Zhuqiang Zhang, Weihong Wang, Xuyu Zhou, Fuping Zhang, Qing Ge, Bing Zhu, Hong Tang, Zhaolin Hua, and Baidong Hou. B Cells Are the Dominant Antigen-Presenting Cells that Activate Naive CD4+ T Cells upon Immunization with a Virus-Derived Nanoparticle Antigen. Immunity 49, 1–14, October 16, 2018.)

It has been well established that the activation of adaptive immune system, in particular, T cells, requires antigen presentation from antigen presenting cells (APCs). Dendritic cells (DCs) are regarded as the “professional” APCs since they are very important if not essential for the activation of naïve T cells. Although B cells express high level of MHC class II and can present antigen to CD4+ T cells, it is considered that B cells only make cognate interactions with activated CD4+ T cells, thus are not involved in the initiation of CD4+ T cell response. In this work, Hou group found that B cells act as the dominant APCs to activate naïve CD4+ T cells when mice were immunized with a type of virus-like particles (VLP), Qb-VLP. Qb-VLP is derived from Q bacterial phage, and is composed 180 copies of single type of monomers. Most importantly, Qb-VLP contains nucleic acids inside which serve as potent TLR ligands. Dr. Hou and colleagues previously showed that TLR signaling in B cells greatly enhanced the Qb-VLP-induced antibody response including germinal center response.

In this study, they developed novel reagent to examine Qb-VLP-induced CD4+ T cell response and the generation of follicular helper T cells (Tfh). They found surprisingly that antigen-specific B cells were both required and sufficient to initiate naïve CD4+ T cell activation, without the requirement of DC function. Qb-specific B cells promoted CD4+ T cell proliferation and differentiation via cognate interactions and through Toll-like receptor signaling-mediated cytokine production. Antigen-specific B cells were also involved in initiating CD4+ T cell responses during immunization with inactivated influenza virus. Their findings have implications for the rational design of nanoparticles as vaccine candidates, particularly for therapeutic vaccines that aim to break immune tolerance.

Prof. Baidong Hou‘s group has been working on the mechanism by which antibody is generated in viral infection and autoimmune diseases. Their goal is to use the knowledge learnt in the basic research to develop novel vaccines and strategy for immune therapy.