Human natural killer (NK) cells express low-affinity Fc immunoglobulin G (IgG) receptor (FcgRIIIA/CD16). The binding of monomeric IgG (mIgG) and F(ab 0 ) 2 fragments of 3G8 anti-CD16 monoclonal antibody (mAb) to FcgRIIIA was investigated by flow cytometry. Over 90% of NK cells bound endogenous IgG, and during incubation at 37 C, the FcgRIIIA occupancy decreased slowly. Approximately 90% of NK cells bind mIgG or F(ab 0 ) 2 fragments of 3G8 anti-CD16 mAb. The calculated half-time (T 1/2 ) of in vitro mIgG dissociation from FcgRIIIA was 130 min. By cross-linking the mIgG ligand with F(ab 0 ) 2 fragments of anti-human IgG antibody, the T 1/2 decreases to 85 min. In kinetics study, it has been shown that 125 I-mIgG bound to FcgRIIIA is slowly released in the culture supernatant, maybe eluted at acid pH, or partially internalized and degraded. The binding of IgG to FcgRIIIA was increased by 53.8% on cells cultured in the presence of RU36156, a matrix metalloproteinase (MMP) inhibitor. Furthermore, an increase in phosphorylation of Lyn tyrosine kinase, after cross-linking of mIgG-FcgRIIIA complex, was observed on NK cells treated with RU36156. When the FcgRIIIA was occupied by mIgG, the capacity of NK cells to kill K562 target cells was decreased by RU36156, because the MMP inhibitor protects CD16 from proteolysis. Our data demonstrate that binding of mIgG to human NK cells is followed by ligand dissociation and/or internalization, enzymatic degradation and exocytosis. The RU36156 MMP inhibitor protects FcgRIIIA from cleavage, augments NK-cell activation and may interfere in their killing capacity.

Receptors for the Fc region of IgG (Fc + RIIIa, Fc + RIIc) and IgM (Fc ? R) were previously described on NK cells. In this work the expression of Fc receptors for IgA (Fc § R) on human NK cells and the signaling events were investigated. The Fc § R was demonstrated by flow cytometry using secretory IgA (sIgA) and anti-human IgA antibody.

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