AUTHOR=Mastelic-Gavillet Beatris , Vono Maria , Gonzalez-Dias Patrícia , Ferreira Frederico Moraes , Cardozo Lucas , Lambert Paul-Henri , Nakaya Helder I. , Siegrist Claire-Anne 

TITLE=Neonatal T Follicular Helper Cells Are Lodged in a Pre-T Follicular Helper Stage Favoring Innate Over Adaptive Germinal Center Responses

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01845

DOI=10.3389/fimmu.2019.01845

ISSN=1664-3224

ABSTRACT=<p>T follicular helper (T<sub>fh</sub>) 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<sub>fh</sub> cells at the transcriptomic level and demonstrated that the T<sub>fh</sub> cell program is well-initiated in neonates although the T<sub>fh</sub> gene-expression pattern (i.e., <italic>CXCR5, IL-21, BCL6, TBK1, STAT4, ASCL2</italic>, and <italic>c-MAF</italic>) is largely underrepresented as compared to adult T<sub>fh</sub> cells. Importantly, we identified a TH2-bias of neonatal T<sub>fh</sub> cells, with preferential differentiation toward short-lived pre-T<sub>fh</sub> effector cells. Remarkably, adjuvantation with CpG-ODNs redirect neonatal pre-T<sub>fh</sub> cells toward committed GC-T<sub>fh</sub> cells, as illustrated by increased expression of T<sub>fh</sub> signature genes and reduced expression of TH2-related genes.</p>