Fig. 3: Beyond the innate/adaptive paradigm, continuing education by adjuvants.
The innate immune system sensing adjuvants and programming the ensuing adaptive immune responses is the current model of how adjuvants function. Activated dendritic cells (DCs) present antigens to naïve antigen-specific CD4+ T helper cells (TH cells) in T cell areas. Some activated TH cells upregulate CXCR5, which mediates their migration to the interface between the B cell follicle and the T cell area, where they express IL-21 and CD40L that stimulate the clonal expansion of antigen-activated B cells. Although some antigen-specific B cells migrate to the medullary cords and differentiate into short-lived plasma cells, other activated B cells migrate into B cell follicles to form germinal centres (GCs). B cells in GCs can subsequently differentiate into memory B cells that recirculate, or long-lived plasma cells (LLPCs) that migrate to the bone marrow. Many adjuvants are known to work primarily by targeting DCs to induce their activation and antigen presentation, but emerging studies demonstrate that adjuvants such as Toll-like receptor (TLR) ligands can also target B cells. Therefore, potentially novel adjuvant targets could include B cell subsets in GCs, bone marrow LLPCs and other cell types that aid survival of LLPCs, follicular DCs (FDCs) and T follicular helper cells (TFH cells). MHC, major histocompatibility complex; TCR, T cell receptor.
