Tfh cell response in influenza vaccines in humans: what is visible and what is invisible

Elucidating the immune mechanism by which seasonal influenza vaccines induce a protective immune response is of great importance to gain insights into the design of next-generation vaccines conferring more effective and long-lasting immune protection. Recent studies have established that T follicular helper (Tfh) cells play a major role for the generation of antibody response following influenza vaccination. Yet, the evidence is gained largely through the analysis of blood samples, and our knowledge on the role of Tfh cells in influenza vaccination is still largely limited to the generation of antigen-specific plasmablasts. Recently, influenza vaccination was shown to induce the expansion of two types of memory B cells in addition to plasmablasts. It is plausible that activated Tfh cells that remain in the lymph nodes after vaccination, a cell population missed in the analysis of blood samples, might also contribute to the diversification of memory B cell repertoire. However, current evidence shows no increase of somatic hypermutation of the expanded memory B cell clones, suggesting that this mechanism is not efficiently active in current influenza vaccines.