Soluble FcγRIIIa is present in plasma and is derived from natural killer cells

FcγRIII (CD16), a receptor for complexed IgG, is encoded by two very homologous genes: FcγRIIIA and FcγRIIIB. NK cells and macrophages express FcγRIIIa, whereas only neutrophils constitutively express FcγRIIIb. In a previous study we found that soluble (s)FcγRIII in plasma seemed to originate only from neutrophils. However, CD16 mAb, directed against different epitopes of FcγRIII, precipitated a glycoprotein from plasma of homozygous FcγRIIIB gene-deficient donors. This glycoprotein migrated in a similar way as did released FcγRIIIa derived from NK cells, whereas FcγRIIIa released by cultured monocytes migrated differently and appeared to be more heavily glycosylated on SDS-PAGE. After deglycosylation, the M(r) of the plasma sFcγRIIIa was similar to that of released FcγRIIIa. Moreover, V8-protease maps were identical. Therefore, we conclude that sFcγRIIIa is also present in plasma and is derived from NK cells. Because sFcγRIII levels are hardly detectable in the plasma of most homozygous FcγRIIIB gene- deficient donors, we suspect that the sFcγRIIIa level is negligible compared with the level of sFcγRIIIb in plasma of healthy donors. Two patients with an NK cell lymphocytosis had a high plasma level of sFcγRIIIa(NK). Furthermore, high levels of sFcγRIIIa(NK) were found in plasma of two patients with rheumatoid arthritis. Thus, the level of sFcγRIIIa(NK) might reflect either an increase in circulating NK cells or an enhanced release of FcγRIIIa(NK) in certain diseases. This study shows that an assay that discriminates between sFcγRIIIa and sFcγRIIIb is necessary for the interpretation of sFcγRIII levels in patients.