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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.

Original publication




Journal article


Nat Immunol

Publication Date





35 - 43


Animals, B-Lymphocytes, Cell Communication, Cells, Cultured, Germinal Center, Humans, Immunophenotyping, Interleukins, Mice, Mice, Inbred C57BL, Mice, Knockout, Natural Killer T-Cells, Phenotype, Proto-Oncogene Proteins c-bcl-6, T-Lymphocytes, Helper-Inducer