IgG‐binding sites on macrophage cell membrane. I. Identification of two distinct Fc receptors on mouse peritoneal macrophages

Abstract

Evidence is presented concerning the existence on mouse peritoneal macrophages of two separate and distinct Fc receptors, one for cytophilic monomeric IgG (mIgG) and the other for polymeric IgG. The latter Fc receptor recognizes both heat-aggregated IgG and antigen-complexed IgG. The major findings of our studies are: (a) the different susceptibility of the two Fc receptor types by pronase, trypsin or phospholipase C; (b) the independent modulation of these two binding sites on the cell membrane; (c) the inability of mIgG to inhibit the binding of particulate antigen-complexed IgG ligand; (d) the ability of mIgG molecules which are devoid of the cytophilic property to attach to the macrophage surface upon their polymerization induced by heating or antigen. The results are discussed in terms of "cytophilic" and "opsonic" Fc receptor types which may provide different functional abilities for normal macrophages.

Cytophilic immunoglobulins revisited via natural killer cells

“…More recent studies with genetically engineered human IgG have indicated that the cytophilic property of human IgGi for FcyRI is an intrinsic property of the C'y2 domain located primarily in the sequence 234-237 proximal to the hinge region, and that in addition to this primary contact site, there are secondary sites involving residues from the carboxyl terminus of the Cy2 domain (17). These data are in good agreement with other reported observations obtained by molecular biologic techniques (e.g., ref 18 Direct and conclusive evidence that the parameters of binding of cytophilic mIgG to Fc'yR are different from those involved in the attachment of opsonic pIgG to Fc'yR-bearing cells was first provided by our studies that indicated two distinct FeyR on mouse activated peritoneal macrophages, one binding mIgG ("cytophilic" Fc'yR) and the other pIgG ("opsonic" FcyR) (20). Quantitative assessment of the binding of human or rabbit IgG to murine FcyR macrophages indicated that the monomeric '251-labeled IgG ligands able to interact with FcyR+ macrophages represented only a mi-SULICA AND HERBERMAN nor fraction (3-5%) of the total IgG (20 (20).…”

“…These data are in good agreement with other reported observations obtained by molecular biologic techniques (e.g., ref 18 Direct and conclusive evidence that the parameters of binding of cytophilic mIgG to Fc'yR are different from those involved in the attachment of opsonic pIgG to Fc'yR-bearing cells was first provided by our studies that indicated two distinct FeyR on mouse activated peritoneal macrophages, one binding mIgG ("cytophilic" Fc'yR) and the other pIgG ("opsonic" FcyR) (20). Quantitative assessment of the binding of human or rabbit IgG to murine FcyR macrophages indicated that the monomeric '251-labeled IgG ligands able to interact with FcyR+ macrophages represented only a mi-SULICA AND HERBERMAN nor fraction (3-5%) of the total IgG (20 (20). This type of experiment, to define the maximum percentage of ligands bound to target cells, was later used by Trucco and dePetris (21) for various murine monoclonal antibodies (mAbs), whose maximum target uptake was found to vary from 15-20% to 65-70% depending on the iodination method used for radiolabeling.…”

“…As a third major line of investigation regarding the difference between binding parameters of mIgG vs. pIgG, we performed studies with FcyR+ mouse macrophages and rabbit IgG anti-sheep red blood cells (SRBC) (20). The rabbit IgG population could be depleted of cytophilic antibody molecules by serial absorptions with FcyR-bearing cells and consequently lose its capacity to react in soluble monomeric form with cytophilic FcyR.…”

Suppression of Contact Sensitivity by IgG1 Antihapten Antibody

“…Treatment for longer than 6 h before antigen stimula tion caused no suppression. Therefore, the suppres sive activity of the antibody could be cleared within 6 h in the culture system and the lymph node cells would become reactive to the antigen stimulation [25].…”

Surface markers of resting and activated human T cells. Functional implications and experimental limits

“…FcTR present on T cells are resistant to trypsin, but sensitive to relatively high concentrations of pronase [32]. Since FcTR present on monocytes, granulocytes, and on variable proportions of null cells are pronase resistant [10], it is conceivable that FcTR present on different cell types may display structural differences, alternatively, two different types of Fc7R may be simultaneously present on certain cell types as shown for mouse macrophages [58,61]. Following pronase digestion, FcTR are detectable after 4-6 h and expression is complete after 10 to 12 h [32].…”