Follicular helper T-cell memory: establishing new frontiers during antibody response

The generation of immunological memory during an immune response is a hallmark of the adaptive immune system. Follicular helper T (Tfh) cells are a CD4(+) T-cell subset specialised to regulate antibody response. Emerging evidence suggests that during antibody response, Tfh memory is generated along with the generation of B-cell memory. There are multiple layers for the differentiation and function of memory Tfh cells. Both early committed precursor Tfh cells and effector Tfh cells exiting germinal centres can contribute to the memory Tfh pool. Functionally, memory Tfh cells not only enhance a secondary response upon antigen rechallenge but also circulate to non-draining lymph tissues to differentiate into effector Tfh cells in the face of systemic antigen/pathogen spreading, thus also promoting a primary response. Circulating memory Tfh cells are a valuable marker to monitor the Tfh programme in human autoimmune diseases, infections and vaccinations. Future studies are required to understand the molecular mechanisms determining the commitment and plasticity of Tfh memory and hence the physiological functions of Tfh memory.