Experimental disruption of T follicular helper cells affects germinal center responses and memory T cell generation.
T follicular helper (T FH ) cells are essential for germinal center (GC) formation and long-lived humoral immunity. Here, we used an Il21 fate mapping (Il21-fm) strategy to remove T FH cells from established GCs to disentangle their function from that of other T cells in a temporal manner. We confirm their role in driving proliferation and positive selection of GC B cells but show that GCs can survive the transient absence of T FH cells. After ablation of T FH cells, both the GC response and affinity maturation recover via ingress of new T FH cells. Despite recovery of the B cell response, T FH cell numbers are never fully restored. This feeds through into the T cell memory response, resulting in diminished recall GC responses. This work shows an unappreciated resilience of primary GC responses to perturbations in T FH cells and demonstrates critical memory T cell generation during this phase.
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Webb et al. (2026) studied this question.
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