Functional Studies of Fc Receptor-Bearing Human Lymphocytes: Effect of Treatment with Proteolytic Enzymes

Abstract In order to analyze the role that Fc receptors (FcR) play in spontaneous cell-mediated cytotoxicity (SLMC), lymphocytes from single donors were tested in parallel for their ability to form rosettes with IgG antibody-coated erythrocytes (EA), and to mediate antibody-dependent cytotoxicity (ADCC) and SLMC. Experimental conditions were chosen in which the expression of FcR at the cell surface is altered (i.e., after enzymatic treatment or reaction with immune complexes). Trypsintreated lymphocytes still expressed FcR and were able to mediate ADCC, but SLMC was completely abolished. Pronase treatment, on the contrary, destroyed FcR and both ADCC and SLMC. When the enzyme-treated cells were cultured for up to 48 hr FcR was reexpressed at the cell surface, and both lytic activities were regained. SLMC from B cell-deprived trypsin-treated cells was recovered in culture in spite of the presence of F(ab′)2 anti-human F(ab′)2 antibodies in the culture medium and throughout the test. Moreover, incubation of the trypsintreated cells in medium containing autologous serum could not reconstitute SLMC. When lymphocytes were reacted with immune complexes, a modulation of both ADCC and SLMC was observed. In this case, the lytic activities could not be recovered even after incubation at 37°C. A partial inhibition of the modulation of FcR was observed when the cells were reacted with immune complexes in the absence of Ca++ ion. The possible existence of two different mechanisms operating in ADCC and SLMC is discussed.