Defect in the membrane expression of high affinity 72kD Fcγ receptors on phagocytic cells in four healthy subjects

Three different receptors for the Fc portion of IgG (FcR) have been characterized on human leukocytes. We have identified four healthy members of one family, whose blood phagocytic cells lack functional 72 kD high-affinity FcRI. Their mono-cytes were unable to bind the Fc portion of mouse (m)-IgG2a and of monomeric human IgG, and they were unreactive with two anti-FcRI monoclonal antibodies. Thus, FcRI is either ab-sent, expressed at very low density, or is so structurally altered as to be unable to bind both its ligand and the anti-FcRI anti-bodies. The failure to bind the Fc portion of mIgG2a underlies the previously reported inability of these monocytes to support T cell mitogenesis on OKT3 stimulation. FcRI was not induc-ible upon incubation of their monocytes or neutrophils in gamma interferon. However, their monocytes were able to bind aggregated human IgG, and to phagocytose IgG-coated parti-cles in vitro. Both functions could be blocked with a mono-clonal antibody to the 40-kD low-affinity FcRII and therefore apparently were mediated exclusively through FcRII. This also demonstrates that FcRII can mediate phagocytosis indepen-dently. Despite the FcRI defect, these subjects had no circu-lating immune complexes, no evidence of autoimmune pathol-ogy and no increased susceptibility to infections