Antigen Modulation Confers Protection to Red Blood Cells from Antibody through Fcγ Receptor Ligation

Abstract

Autoantibodies and alloantibodies can damage self-tissue or transplanted tissues through either fixation of complement or ligation of FcγRs. Several pathways have been described that imbue self-tissues with resistance to damage from complement fixation, as a protective measure against damage from these Abs. However, it has been unclear whether parallel pathways exist to provide protection from FcγR ligation by bound Abs. In this article, we describe a novel pathway by which cell surface Ag is specifically decreased as a result of Ab binding (Ag modulation) to the extent of conferring protection to recognized cells from Fcγ-dependent clearance. Moreover, the Ag modulation in this system requires FcγR ligation. Together, these findings provide unique evidence of self-protective pathways for FcγR-mediated Ab damage.

Anti-KEL sera prevents alloimmunization to transfused KEL RBCs in a murine model

“…In addition, intracellular RBC staining fails to haematologica 2015; 100:e396 [6][7][8][9] and murine RBC antigen models. [10][11][12] However, the mechanism(s) of modulation appears to vary by antigen.…”

Hemolytic Disease of the Fetus and Newborn: Modern Practice and Future Investigations

“…58 Multiple subtypes of monoclonal antibodies as well as polyclonal antibodies have been investigated, with some but not all being capable of preventing alloimmunization altogether or of decreasing the magnitude of an alloimmune response [59][60][61] . In at least one model, the efficacy of passively infused antibodies at preventing an alloimmune response to transfused RBCs has been shown to be independent of the inhibitory FcRIIb receptor 60 .…”

Examination of Whole Cell Galectin Binding by Solid Phase and Flow Cytometric Analysis

“…In addition, the examination of galectin binding in the linear range of ligand engagement can result in significant inter-assay variability as a result of subtle differences in the concentration of galectins employed in different assay conditions. By contrast, most flow cytometric analyses purposely employ monoclonal antibodies at saturating levels to ensure complete engagement of target ligands in order to adequately identify potential alteration in ligand density between cellular subsets and following potential ligand modifications [22–24]. In addition, flow cytometric analysis does not necessarily provide a measurement of affinity to determine whether, in addition to alterations in ligand density, the actual affinity of galectins toward carbohydrate ligands may differ between unique cell populations decorated with different glycan ligands.…”