Figure 1.

Induction of humoral immunity by utilizing iNKT-licensed B cells and iNKT-licensed dendritic cells (DCs). iNKT cells can provide both direct (A) and DC-mediated (B) help for antigen-specific B cell responses. (A) Innate iNKTfh cells recognize glycolipid antigen-CD1d on B cells and directly provide helper signals. These initiate plasmablast (PB) expansion and germinal center (GC) formation, leading to the primary class-switched antibody (Ab) production. (B) Antigen-expressing artificial adjuvant vector cells [e.g., artificial adjuvant vector cells (aAVC)-hemagglutinin (HA)] are comprised of the CD1d–α-GalCer complex on the surface of the aAVC and HA are expressed in the cytosol. (i) Administration of aAVC-HA initially stimulates iNKT cells. (ii) The aAVC-HA is killed by iNKT cells and NK cells and then HA tumor antigen released from them can be captured by endogenous CD11c⁺ DCs. (iii) The CD11c⁺ DCs then undergo iNKT cell-induced maturation. (iv) The activated DCs can then induce an HA-specific CD4⁺ T cell response. Thus, the CD11c⁺ DCs in situ are able to present HA antigen derived from phagocytosed aAVC-HA to CD4⁺ T cells. (v) On the other hand, B cells also capture HA antigen. B cells can then be stimulated by antigen-specific CD4⁺ T cells, resulting in PB expansion, GC formation, and long-term Ab production.