Abstract
Vaccination with CD1d-binding glycolipid adjuvants and co-administered protein, lipid, and carbohydrate antigens leads to invariant natural killer T (NKT) cell-dependent enhancement of protective B cell responses. NKT cell activation boosts the establishment of protein antigen-specific B cell memory and long-lived plasma cell (LLPC) compartments. NKT cells may exert a similar effect on some carbohydrate-specific B cells, but not lipid-specific B cells. The mechanisms of action of NKT cells on B cell responsiveness and subsequent differentiation into memory B cells and LLPC is dependent on CD1d expression by dendritic cells and B cells that can co-present glycolipids on CD1d and antigen-derived peptide on MHCII. CD1d/glycolipid-activated NKT cells are able to provide help to B cells in a manner dependent on cognate and non-cognate interactions. More recently, a glycolipid-expanded subset of IL-21-secreting NKT cells known as NKT follicular helper cells has been suggested to be a driver of NKT-enhanced humoral immunity. This review summarizes established and recent findings on how NKT cells impact humoral immunity and suggests possible areas of investigation that may allow the incorporation of NKT-activating agents into vaccine adjuvant platforms.
Highlights
Several research groups have demonstrated that CD1d-restricted natural killer T (NKT) cells influence the humoral immune response to viruses, bacteria, their toxins, parasites, and fungi (Table 1)
Prophylactic immunization of a mammal with a vaccine antigen or other pathogen product in combination with a CD1d-binding, NKT-activating adjuvant such as the α-galactosylceramide (α-GC) glycolipid has resulted in the enhancement of pathogen-specific Ab responses
The NKT-enhanced Ab responses are typified by Ig class switch [1,2,3,4], establishment of B cell memory (Bmem) [2, 5], and long-lived plasma cells (LLPC) [6, 7], all hallmarks of a desirable vaccine response
Summary
Several research groups have demonstrated that CD1d-restricted natural killer T (NKT) cells influence the humoral immune response to viruses, bacteria, their toxins, parasites, and fungi (Table 1). Prophylactic immunization of a mammal with a vaccine antigen or other pathogen product in combination with a CD1d-binding, NKT-activating adjuvant such as the α-galactosylceramide (α-GC) glycolipid has resulted in the enhancement of pathogen-specific Ab responses. These NKT-enhanced Ab responses are associated with, or contributory to enhanced protection against lethal challenges with pathogens or their toxins. The NKT-enhanced Ab responses are typified by Ig class switch [1,2,3,4], establishment of B cell memory (Bmem) [2, 5], and long-lived plasma cells (LLPC) [6, 7], all hallmarks of a desirable vaccine response.
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