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… - Nature …, 2012 - nature.com
PP Chang, P Barral, J Fitch, A Pratama, CS Ma, A Kallies, JJ Hogan, V Cerundolo…
Nature immunology, 2012nature.com
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-1hi follicular helper NKT cells (NKTFH cells), and this process required
expression of the transcriptional repressor Bcl-6, signaling via the coreceptor CD28 and …
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-1hi 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 germinal centers, those driven by NKTFH 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.
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