iNKT cells stimulate B cells to produce antibodies against ABO blood group antigens through a mechanism involving the interaction of invariant T-cell receptor–CD1d and the production of IL5. Anti-CD1d mAb blocks antibody production against blood group A antigen, potentially revealing a novel therapeutic strategy for ABO-incompatible transplant recipients, preventing rejection episodes mediated by antibodies against the widely expressed ABO blood group antigens. Professional illustration by Alice Y. Chen.