The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria

Abstract

Fc receptors on phagocytic cells in the blood mediate binding and clearance of immune complexes, phagocytosis of antibody-opsonized microorganisms, and potently trigger effector functions, including superoxide anion production and antibody-dependent cellular cytotoxicity. The Fc receptor type HI (FcγR III, CD 16), present in 135,000 sites per cell 1 on neutrophils and accounting for most of FcR in blood, unexpectedly has a phosphatidylinositol glycan (PIG) membrane anchor. Deficiency of FcγR III is observed in paroxysmal nocturnal haemoglobinuria (PNH), an acquired abnormality of haematopoietic cells2 affecting PIG tail biosynthesis or attachment3, and is prbably responsible for circulating immune complexes4 and susceptibility to bacterial infections associated with this disease5. Although a growing number of eukaryotic cell-surface proteins with PIG-tails are being described6,7, none has thus far been implicated in receptor-mediated endocytosis or in triggering of cell-mediated killing. Our findings on the FcγR III raise the question of how a PIG-tailed protein important in immune complex clearance in vivo8,9 and in antibody-dependent killing10 mediates ligand internalization and cytotoxicity. Together with our results, previous functional studies on FcγR III and FcγR II11,12 suggest that these two receptors may cooperate and that the type of membrane anchor is an important mechanism whereby the functional capacity of surface receptors can be regulated.

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Selvaraj, P., Rosse, W., Silber, R. et al. The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria. Nature 333, 565–567 (1988). https://doi.org/10.1038/333565a0

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