Regulatory mechanism of functional differentiation of immune cells

Follicular helper T (Tfh) cells play essential roles in high-affinity humoral immune responses by supporting differentiation of B cells into memory and plasma cells and their production of high affinity antibodies. Inappropriate regulation of Tfh cell differentiation can cause immune deficiency, allergy, and autoimmune disorders. However, the molecular mechanisms that underlie their differentiation still remain unclear.

In vivo studies of differentiation of Tfh cells indicated that the process of their differentiation can be divided into several stages. In order to analyze the differentiation inducing signals, quantitatively and chronologically in each stage, and to elucidate the molecular mechanism of Tfh cell differentiation, it appears to be important to establish an in vitro Tfh cell differentiation system that almost exactly reflects the in vivo Tfh cell inducing responses. However, there remains no reproducible in vitro Tfh cell differentiation system for murine cells. Therefore, to elucidate the molecular mechanism of Tfh cell differentiation, we aim to establish an in vitro Tfh cell differentiation system for murine T cells by searching for factors, from inside and outside of the body, that are involved in Tfh cell differentiation, and clarifying their roles in the differentiation induction.