title: Cutting edge: dendritic cell-restricted antigen presentation initiates the follicular helper T cell program but cannot complete ultimate effector differentiation.
abstract: Follicular helper T (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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Radhika
authors.initials: R
authors.lastname: Goenka
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Barnett
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Silver
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: O'Neill
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
authors.forename: Terri M
authors.initials: TM
authors.lastname: Laufer
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology* / Q000473:pathology*