Invariant NKT cells sustain specific B cell responses and memory

Invariant natural killer T (iNKT) cells are innate-like lymphocytes recognizing CDid-restricted glycolipid antigens, such as alpha-galactosylceramide (alpha GC). We assessed whether iNKT cells help B lymphocyte responses and found that mice immunized with proteins and aGC develop antibody titers 1-2 logs higher than those induced by proteins alone. Activation of iNKT cells enhances protection against infections such as influenza and elicits higher frequencies of memory B cells and higher antibody responses to booster immunizations. Protein vaccination with alpha GC, but not with conventional adjuvants, elicits IgG responses in mice lacking MHC class 11 molecules, demonstrating that iNKT cells can substitute for CD4(+) T cell help to B cells. Interestingly, the decay of circulating antibodies is faster in mice lacking iNKT cells. These findings point to a homeostatic role for iNKT cells on critical features of the antibody response such as immunity and B cell memory.