Using traceable immunization and pathogen infection models, the TFH differentiation process can be divided into three spatiotemporal phases: (1) Initiation of TFH differentiation by DC priming of naïve CD4+ T cells in the T cell zone of the secondary lymphoid organs; (2) TFH maturation induced by interactions with cognate B cells at the T-B border; and (3) the functional/maintenance phase, within the GC [reviewed in (37, 38)]. This evidence concerns the gene CD4 and infection.