Cutting Edge: Dendritic Cell-Restricted Antigen Presentation Initiates the Follicular Th Cell Program but Cannot Complete Ultimate Effector Differentiation

Abstract

Follicular Th (T_FH) cells are critical for germinal center (GC) formation. The processes that drive their generation and effector potential remain unclear. In this study, we define requirements for MHC class II APCs in murine T_FH cell formation by either transiently ablating or restricting Ag presentation to dendritic cells (DCs). We find that cognate interactions with DCs are necessary and sufficient to prime CD4⁺ T cells toward a CXCR5⁺ICOS⁺Bcl6⁺ T_FH cell intermediate. However, in the absence of additional APCs, these T_FH cells fail to produce IL-21. Furthermore, in vitro priming of naive T cells by B cells engenders optimal production of IL-21, which induces a GC B cell transcriptional profile. These results support a multistep model for effector T_FH cell priming and GC initiation, in which DCs are necessary and sufficient to induce a T_FH cell intermediate that requires additional interactions with distinct APCs for full effector function.