The regulation and role of T follicular helper cells in immunity

It is well established that the generation of a high-affinity long-lived antibody response requires the presence of T cells, specifically CD4(+) T cells. These CD4(+) T cells support the generation of a germinal centre (GC) response where somatic hypermutation and affinity maturation take place leading to the generation of memory B cells and plasma cells, which provide long-lasting protection. Greater insight into the nature of the CD4(+) T cells involved in this process was provided by two studies in 2000 that described CD4(+) T cells residing in the B cell follicle that expressed CXCR5. As a result these cells were named follicular B helper T cells, now more commonly known as T follicular helper (Tfh) cells. Since then there has been enormous growth in our understanding of these cells, now considered a distinct T helper (Th) cell lineage that can arise from naive CD4(+) T cells following activation. This review summarizes some of the most recent work that has characterized Tfh cells and the pathways that lead to their generation.