iNKT‐cell help to B cells: A cooperative job between innate and adaptive immune responses

T‐cell help to B lymphocytes is one of the most important events in adaptive immune responses in health and disease. It is generally delivered by cognate CD4⁺ T follicular helper (T_FH) cells via both cell‐to‐cell contacts and soluble mediators, and it is essential for both the clonal expansion of antibody (Ab)‐secreting B cells and memory B‐cell formation. CD1d‐restricted invariant natural killer T (iNKT) cells are a subset of innate‐like T lymphocytes that rapidly respond to stimulation with specific lipid antigens (Ags) that are derived from infectious pathogens or stressed host cells. Activated iNKT cells produce a wide range of cytokines and upregulate costimulatory molecules that can promote activation of dendritic cells (DCs), natural killer (NK) cells, and T cells. A decade ago, we discovered that iNKT cells can help B cells to proliferate and to produce IgG Abs in vitro and in vivo. This adjuvant‐like function of Ag‐activated iNKT cells provides a flexible set of helper mechanisms that expand the current paradigm of T‐cell–B‐cell interaction and highlights the potential of iNKT‐cell targeting vaccine formulations.