Neonatal T follicular helper cells are lodged in a pre-T follicular helper stage favoring innate over adaptive germinal center responses

Follicular T helper (T FH ) cells have emerged as a critical limiting factor for controlling the magnitude of neonatal germinal center (GC) reactions and primary vaccine antibody responses. We compared the functional attributes of neonatal and adult T FH cells at the transcriptomic level and demonstrate that the T FH cell program is well initiated in neonates although the T FH gene-expression pattern (i.e. CXCR5, IL-21, Bcl6, TBK1, STAT4, Ascl2 and c-maf) is largely underrepresented as compared to adult T FH cells. Importantly, we identified a dominant T H2 - bias of neonatal T FH cells, with preferential differentiation toward short-lived pre-T FH effector cells. Remarkably, adjuvantation with CpG-ODNs redirect neonatal pre-T FH cells toward committed GC-T FH cells, as illustrated by increased expression of T FH signature genes and reduced expression of T H2 -related genes. A total of 12 samples: 4 groups with 3 biological replicates each.