T Follicular Helper Cell Dynamics in Germinal Centers

T follicular helper (T-FH) cells are a specialized subset of effector T cells that provide help to and thereby select high-affinity B cells in germinal centers (GCs). To examine the dynamic behavior of T-FH cells in GCs in mice, we used two-photon microscopy in combination with a photoactivatable fluorescent reporter. Unlike GC B cells, which are clonally restricted, T-FH cells distributed among all GCs in lymph nodes and continually emigrated into the follicle and neighboring GCs. Moreover, newly activated T-FH cells invaded preexisting GCs, where they contributed to B cell selection and plasmablast differentiation. Our data suggest that the dynamic exchange of T-FH cells between GCs ensures maximal diversification of T cell help and that their ability to enter ongoing GCs accommodates antigenic variation during the immune response.