Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses.
Chang P-P., Barral P., Fitch J., Pratama A., Ma CS., Kallies A., Hogan JJ., Cerundolo V., Tangye SG., Bittman R., Nutt SL., Brink R., Godfrey DI., Batista FD., Vinuesa CG.
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.