With a Little Help from T Follicular Helper Friends: Humoral Immunity to Influenza Vaccination

Influenza remains a global and unpredictable threat. Annual vaccination against influenza A and B viruses promotes the induction of Abs and memory B cells, which can provide strain-specific protection against subsequent infections. The formation of effective memory B cell and Ab responses is highly dependent on the germinal center reaction, a well-orchestrated process involving B cells and a specialized CD4(+) T cell subset called T follicular helper (Tfh) cells. As Tfh cells predominantly reside within B cell follicles in secondary lymphoid organs, they are challenging to study in humans. Recent identification of a circulating counterpart of Tfh cells has allowed us to better understand the contribution of these circulating Tfh cells during human immune responses. In this article, we summarize the role of human Tfh cells during humoral immune responses and discuss the contribution of Tfh cells in promoting immunity to influenza viruses in healthy cohorts and high-risk groups.