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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.

Type Journal
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.;
Published Date 2012-01-31
Published Volume 13
Published Issue 1
Published Pages 35-43
Status Published in-print
DOI 10.1038/ni.2166 ni.2166 [pii]
URL link to publisher's version
OpenAccess link to author's accepted manuscript version