Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses

PP Chang; P Barral; J Fitch; A Pratama; CS Ma; A Kallies; JJ Hogan; V Cerundolo; SG Tangye; R Bittman; SL Nutt; R Brink; DI Godfrey; FD Batista; CG Vinuesa

Journal article

Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses

PP Chang, P Barral, J Fitch, A Pratama, CS Ma, A Kallies, JJ Hogan, V Cerundolo, SG Tangye, R Bittman, SL Nutt, R Brink, DI Godfrey, FD Batista, CG Vinuesa

Nature Immunology | Published : 2012

DOI: 10.1038/ni.2166

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 (NKTFH cells), and this process required expression of the transcriptional repressor Bcl-6, signaling via the coreceptor CD28 and interaction with B cells. NKTFH cells provided direct cognate help to antigen-specific B cells that was dependent on interleukin 21 (IL-21). Unlike T cell-dependent..

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University of Melbourne Researchers

Axel Kallies Author

Stephen Nutt Author

Dale Godfrey Author

Grants

Awarded by Sylvia and Charles Viertel Charitable Foundation

Funding Acknowledgements

We thank the US National Institutes of Health Tetramer Core Facility for the allophycocyanin-conjugated mouse CD1d-alpha-GalCer tetramer; M. Kronenberg (La Jolla Institute for Allergy and Immunology) for the baculovirus construct; P. Savage (Brigham Young University) for alpha-GalCer (PBS44); M. Taniguchi (RIKEN Research Center for Allergy and Immunology) for J<INF>alpha</INF>18-deficient mice; M. Townsend for tissue sectioning; X. Hu, M. Srivastava and J. Ellyard for help with some experiments; and M. Pellegrini for infection of mice with L. monocytogenes. Supported by the Sylvia and Charles Viertel Charitable Foundation (C.G.V.), the European Commission (Seventh Framework Programme of the European Commission PIEF-GA-2008-220863 to P.B.), Cancer Research UK (F.D.B. and P.B.), the Royal Society (F.D.B.), the National Health and Medical Research Council of Australia (D.I.G., C.G.V., R.B., C.S.M. and S.G.T.) and the Australian Research Council (A.K.).