On transfusion of HOD RBCs at a high dose (109) in mice, in the presence of anti-Duffy alone (left side), alloimmunization (anti-HEL IgG formation) is significantly enhanced. Anti-Duffy increases RBC antigen removal, RBC clearance, and CD4+ T-cell proliferation. Notably, antibody-mediated RBC clearance may enhance de novo alloimmunization. On transfusion of HOD RBCs at a high dose (109) in mice, in the presence of the combination of anti-Duffy and anti-HEL (right side), the enhanced anti–Duffy-mediated RBC alloimmune response is overturned by anti-HEL into AMIS. Anti-HEL increases RBC antigen removal but does not impact RBC clearance and CD4+ T-cell proliferation. Figure created with BioRender.com. OVA, ovalbumin.