Dynamic regulation of Bcl6 in follicular helper CD4 T (Tfh) cells

•Bcl6 expression is regulated by complex signaling circuitries in CD4 T cells.•The signaling pathways that regulate Bcl6 expression in positive and negative ways are discussed in detail.•Future studies are suggested to reveal more clearly how Bcl6 is regulated in CD4 T cells, which will contribute to better vaccine development.

Our bodies are continuously exposed to various types of infectious pathogens. Vaccinations are the most cost effective way to protect our bodies against a variety of infectious microbes. The efficacy of most vaccines relies on protective antibody production and generation of memory B cells. These two key components develop mostly from B cells that participate in germinal center reactions. Recent efforts have highlighted the critical role of follicular helper CD4 T (Tfh) cells in the generation of germinal centers. Given that Bcl6 is a major transcription factor for Tfh differentiation, here we review recent developments in the understanding of signaling molecules that regulate Bcl6 expression in CD4 T cells, as a potential target for development of more efficacious vaccines.