Follicular Th (TFH) 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 TFH 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+ TFH cell intermediate. However, in the absence of additional APCs, these TFH 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 TFH cell priming and GC initiation, in which DCs are necessary and sufficient to induce a TFH cell intermediate that requires additional interactions with distinct APCs for full effector function.
This work was supported by Veterans Administration Merit Award BX000435 (to T.M.L.),National Institutes of Health Grants R01 AI 42334 (to C.A.H.), and R01 AI 073939 (to M.P.C.). R.G. was supported by National Institutes of Health Training Grant T32 AI 055428. J.S.S. is supported by National Institutes of Health Training Grant T32 AI 007532.
The online version of this article contains supplemental material.
- Received March 28, 2011.
- Accepted June 7, 2011.