Glycolipid-activated NKT cells support the induction of persistent plasma cell responses and antibody titers

NKT cell activation with CD1d-binding glycolipid alpha-galactosylceramide (alpha-GC) enhances antibody responses to co-administered T-dependent antigen. The efficacy of alpha-GC relative to other CD1d-binding glycolipids and adjuvants is not known. There is little information on how NKT cells affect antibody production beyond initial booster-stimulated recall responses. We therefore tested the hypothesis that alpha-GC stimulates induction of plasma cells and antibody responses as effectively as Th1- and Th2-skewing variants of alpha-GC and several other adjuvants. C57BL/6 and CD1d-/- mice were immunized with nitrophenol-conjugated keyhole limpet hemocyanin (NP-KLH) plus alpha-GC or NP-KLH plus adjuvants before administration of an NP-KLH booster and assessing antibody responses and plasma cell frequency. alpha-GC boosted long-term antibody responses as efficiently as all other agents tested and induced plasma cells that were detected in bone marrow 13 weeks after immunization. We then determined whether NKT cells were required in the presence of other adjuvants. CD1d-/- mice had a reduced induction of plasma cells in response to NP-KLH/Alum as compared to C57BL/6 mice. However, NKT cells were not required for the continued presence of those cells that were induced. Although NKT cells are capable of inducing persistent plasma cell responses, they may not play a major role in supporting longevity post-induction.