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

Invariant NKT cells elicit the rapid release of cytokines. Two papers by Leadbetter and Vinuesa and colleagues show that these cells can also provide direct help to B cells to elicit rapid antibody responses. 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.