Abstract
BACKGROUND: IgG against alloantigens on transfused RBC can lead to antibody-mediated immune enhancement (AMIE). AMIE has properties not found in other forms of alloimmunization, including rapid clearance of RBCs, a requirement for Fc-gamma receptors on dendritic cells, and no dependence on IFNAR. A spleen is required for alloimmunization to transfused RBCs under normal conditions but its role in AMIE has not been assessed. STUDY DESIGN AND METHODS: Mice with surgical splenectomy or sham surgery were infused with monoclonal IgG against model antigens (HOD or KEL) followed by a transfusion of respective transgenic RBCs. Antibody binding to transfused RBCs, antigen-modulation, and RBC clearance were assessed by flow cytometry. IgM and IgG to the HOD and KEL alloantigens were quantified by flow cytometry-based crossmatch. RESULTS: IgG to either HOD or KEL caused brisk clearance of RBCs with almost complete antigen modulation at 24 h and a strong enhancement of both IgM and IgG in sham-operated animals. In splenectomized animals, AMIE was eliminated; antigen-modulation occurred but with decreased kinetics and magnitude; and RBC clearance was the same as in sham animals. CONCLUSIONS: The current study extends the role of spleen as a general requirement for all known pathways of RBC alloimmunization studied thus far. However, the dissociation of clearance and antigen-modulation from AMIE shown in the current study raises the possibility that antigen-modulation and AMIE are correlated due to a confounding common cause (i.e., IgG binding RBCs).