AUTHOR=Trüb Marta , Barr Tom A. , Morrison Vicky L. , Brown Sheila , Caserta Stefano , Rixon Jordan , Ivens Alasdair , Gray David 

TITLE=Heterogeneity of Phenotype and Function Reflects the Multistage Development of T Follicular Helper Cells

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00489

DOI=10.3389/fimmu.2017.00489

ISSN=1664-3224

ABSTRACT=<p>T follicular helper cells (Tfh) provide crucial signals for germinal center (GC) formation, but Tfh populations are heterogeneous. While PD1<sup>hi</sup> Tfh are important in the GC response, the function of the PD1<sup>lo</sup> Tfh-like subset is unknown. We show that these cells, like the PD1<sup>hi</sup> GC–Tfh, depend upon B cells; however, their entry to follicles is independent of CXCR5 or cognate interactions with B cells. The differentiation into PD1<sup>hi</sup> Tfh is dependent on MHC class II interactions with B cells and requires CXCR5. Our data suggest a Tfh differentiation pathway that is initially B cell-independent, then dependent on non-cognate B cell interactions, and finally following cognate interaction with B cells and CXCR5-ligands allows the formation of GC–Tfh. The PD1<sup>lo</sup> Tfh-like cells make early cytokine responses and may represent precursors of CD4 memory cells.</p>