Hypotheses explaining AMIS-induced RBC antigen loss via trogocytosis. (A) Destruction of the RBC: IgG-sensitized RBCs interact with immune cells (macrophages, B cells, neutrophils, and dendritic cells), which strip the antigen-antibody complex from the surface of the RBC along with RBC membrane resulting in extensive cell damage. (B) RBC antigen loss: IgG-sensitized RBCs undergo trogocytosis-induced antigen loss by an immune cell (macrophages, B cells, neutrophils, and dendritic cells), resulting in circulating RBCs with an antigen level below that needed for an immune response. (C) Deviation of the immune response: IgG-sensitized RBCs engage with an antigen presenting cell (macrophages, dendritic cells, or B cells), resulting in the internalization of the IgG-antigen complex with peptides from both the antigen and IgG, which compete for display on major histocompatibility complex class II. Under AMIS conditions, the IgG peptides preferentially undergo antigen processing and presentation to T helper cells. This figure was created with BioRender.com.