Invariant natural killer T (iNKT) cells serve as early rapid responders in the innate recognition of both self and foreign antigens. iNKT cells have been demonstrated to both enhance and negatively regulate B cell activation. The negative regulation has been shown to be induced during auto-inflammation in response to syngeneic apoptotic cells and inflammasome activation in response to the innate cytokine IL-18. Mechanistically, IL-18 activated iNKT cells regulate self-reactive B cell activation by preventing B cell entry into the germinal center. We have recently shown that this pathway involves neutrophils that license the iNKT cells to regulate B cells through FAS ligand mediated killing. Since activation of iNKT cells using exogenous glycolipid agonists has shown great clinical potential, we investigated whether iNKT cells exert their regulatory function and how iNKT cells respond to exogenous glycolipids during inflammation in response to IL-18. We find that exogenous glycolipids disrupt the regulatory cellular cooperation between neutrophils and iNKT cells and that iNKT cells get activated to become iNKT follicular helper cells. This in effect enhances the autoreactive B cell response including production of auto-antibodies. These findings have relevance for autoimmune diseases where infections and vaccination using glycolipids that provide ligands for iNKT cells could disrupt a potentially important negative regulatory loop and allow for autoreactive B cells to enter the germinal center.