Saturable, high-avidity monocyte receptors for monomeric IgG and Fc fragments increase in SLE and lyme disease.
We have devised an assay for quantifying high-avidity Fc receptors for monomeric IgG on peripheral blood monocytes. In the development of a radiolabelled ligand for the assay, we found that Fc fragments offer several advantages over 7S-IgG. Compared to the latter ligand, the fragments interacted more cleanly with a single high-avidity binding site, appeared to have easier access to this site, and, since they showed no binding to Millipore filters, their use made possible a wash procedure that was convenient and rapid, thus minimizing loss of specifically bound ligand. Application of the assay to a study of ten normal controls, five patients with SLE, and three patients with Lyme disease demonstrated that normal monocytes bear approximately 10,000 high-avidity binding sites per cell. In contrast, patient monocytes bore significantly more Fc receptors; on average their cells had about 40,000 such sites per cell (P = 0.01) and sometimes as many as 100,000 sites per cell. Both normal and patient monocytes bound IgG or Fc fragments with an apparent association constant (KA) of approximately 10(8) M-1. The majority of patients with active SLE and Lyme disease had serum C1q-binding material compatible with the presence of circulating immune complexes. This study shows that these putative circulating immune complexes do not necessarily lead to a reduction in the number of Fc receptors on peripheral blood monocytes. Rather, the data suggest that in the course of immune mediated diseases, either monocytes are activated in vivo to express greater numbers of Fc receptors, or a subset of monocytes bearing more Fc receptors is expanded.
D000915:Antibody Affinity; D000936:Antigen-Antibody Complex / Q000032:analysis; D002469:Cell Separation; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000032:analysis*; D007128:Immunoglobulin Fragments / Q000032:analysis*; D007074:Immunoglobulin G / Q000032:analysis*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D011869:Radioligand Assay / Q000379:methods; D011961:Receptors, Fc / Q000032:analysis*; D017452:Receptors, IgG; D011971:Receptors, Immunologic / Q000032:analysis*
D000936:Antigen-Antibody Complex; D007141:Immunoglobulin Fc Fragments; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic