Memory Follicular Helper Invariant NKT Cells Recognize Lipid Antigens on Memory B Cells and Elicit Antibody Recall Responses

Invariant NKT (iNKT) cells have been shown to help B cells in a cognate or noncognate manner; however, whether cognate iNKT cell help induces B cell memory responses remains controversial, and the underlying mechanisms are still unclear. In this study, we demonstrated that, in the absence of follicular helper T cells, cognate iNKT cell help could promote B cell memory responses in mice that were dependent on the formation of memory follicular helper iNKT (iNKT FH ) cells and their interactions with memory B cells in recall responses. Generation of memory iNKT FH cells required lipid Ag presentation by dendritic cells but not by B cells. Upon rechallenge, memory iNKT FH cells recognized lipid Ags presented by memory B cells, which recalled iNKT FH effector cells and elicited B cell memory responses. However, LPS, which promoted the synthesis of self-lipids, failed to elicit recall responses in the absence of exogenous lipid Ags.