title: Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses.
abstract: Lipid antigens trigger help from natural killer T cells (NKT cells) for B cells, and direct conjugation of lipid agonists to antigen profoundly augments antibody responses. Here we show that in vivo, NKT cells engaged in stable and prolonged cognate interactions with B cells and induced the formation of early germinal centers. Mouse and human NKT cells formed CXCR5(+)PD-1(hi) follicular helper NKT cells (NKT(FH) cells), and this process required expression of the transcriptional repressor Bcl-6, signaling via the coreceptor CD28 and interaction with B cells. NKT(FH) cells provided direct cognate help to antigen-specific B cells that was dependent on interleukin 21 (IL-21). Unlike T cell-dependent germinal centers, those driven by NKT(FH) cells did not generate long-lived plasma cells. Our results demonstrate the existence of a Bcl-6-dependent subset of NKT cells specialized in providing help to B cells.
authors: Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors: Pheh-Ping
authors: PP
authors: Chang
authors: Patricia
authors: P
authors: Barral
authors: Jessica
authors: J
authors: Fitch
authors: Alvin
authors: A
authors: Pratama
authors: Cindy S
authors: CS
authors: Ma
authors: Axel
authors: A
authors: Kallies
authors: Jennifer J
authors: JJ
authors: Hogan
authors: Vincenzo
authors: V
authors: Cerundolo
authors: Stuart G
authors: SG
authors: Tangye
authors: Robert
authors: R
authors: Bittman
authors: Stephen L
authors: SL
authors: Nutt
authors: Robert
authors: R
authors: Brink
authors: Dale I
authors: DI
authors: Godfrey
authors: Facundo D
authors: FD
authors: Batista
authors: Carola G
authors: CG
authors: Vinuesa
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D051560:Proto-Oncogene Proteins c-bcl-6; D000098546:Interleukin-21