Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner

Nat Immunol. 2011 Nov 27;13(1):44-50. doi: 10.1038/ni.2172.


Mouse invariant natural killer T cells (iNKT cells) provide cognate and noncognate help for lipid and protein-specific B cells, respectively. However, the long-term outcome for B cells after cognate help is provided by iNKT cells is unknown at present. Here we found that cognate iNKT cell help resulted in a B cell differentiation program characterized by extrafollicular plasmablasts, germinal-center formation, affinity maturation and a robust primary immunoglobulin G (IgG) antibody response that was uniquely dependent on iNKT cell-derived interleukin 21 (IL-21). However, cognate help from iNKT cells did not generate an enhanced humoral memory response. Thus, cognate iNKT cell help for lipid-specific B cells induces a unique signature that is a hybrid of classic T cell-dependent and T cell-independent type 2 B cell responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology*
  • B-Lymphocytes / immunology*
  • Germinal Center / immunology
  • Immunity, Humoral
  • Immunologic Memory
  • Interleukins / physiology*
  • Lipids / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Killer T-Cells / immunology*
  • Receptors, Antigen, B-Cell / immunology
  • Signal Transduction / immunology
  • Spleen / immunology


  • Antigens
  • Interleukins
  • Lipids
  • Receptors, Antigen, B-Cell
  • interleukin-21