Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses
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||Chang, P. P.; Barral, P.; Fitch, J.; Pratama, A.; Ma, C. S.; Kallies, A.; Hogan, J. J.; Cerundolo, V.; Tangye, S. G.; Bittman, R.; Nutt, S. L.; Brink, R.; Godfrey, D. I.; Batista, F. D.; Vinuesa, C. G.;|
|Publisher Name||NATURE IMMUNOLOGY|
|DOI||10.1038/ni.2166 ni.2166 [pii]|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22120117|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/11087|