Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses

Nat Immunol. 2011 Nov 27;13(1):35-43. doi: 10.1038/ni.2166.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Interleukins
  • Proto-Oncogene Proteins c-bcl-6
  • interleukin-21