Heterogeneity of human lymphocyte Fc receptors: Studies using heat-aggregated and antigen-complexed IgG from human, rabbit, guinea pig, horse and goat

Abstract

We have studied the ability of human peripheral blood lymphocytes (HuPBL) 4 to interact with IgG from several animal species. Three functions or activities that are reported to depend on an interaction between complexed IgG and HuPBL receptors (R) for the Fc piece of IgG (FcγR) were compared: (1) antibody-dependent cell-mediated cytotoxicity (ADCC); (2) binding of heat-aggregated IgG (aggG); and (3) rosette formation with IgG-sensitized erythrocytes [RBC-A(γ)]. IgG (and IgM) antibodies to chicken erythrocytes (CRBC) were purified from the sera of the following species after injection with CRBC stroma: (1) horse (Ho); (2) goat (Go); (3) rabbit (Ra); and (4) guinea pig (Gp). Good IgG-agglutinating antibody titers were obtained from each injected species. Using 51Cr-labeled CRBC targets and HuPBL effector cells, only Ra anti-CRBC IgG gave good ADCC at high dilutions. Ho and Go anti-CRBC (IgG) failed to give AD̄CĊ, and Ḡp anti-CRBC (IgG) gave approx. 30% of the level of kill as Ra. Ra Fab' 2 fragments of IgG antibody failed to produce ADCC. Treatment of HuPBL with Ra anti-lymphocyte serum (ALS) almost totally ablated ADCC, whereas HoALS failed to alter ADCC. Pretreatment of HuPBL with aggG showed that Ra or Hu aggG gave essentially equal inhibition of ADCC, Gp gave approx. 30% of the degree of inhibition as Hu and Ra, and Ho or Go aggG had essentially no effect of ADCC. These results confirmed the following order of ability of IgG to interact with HuPBL ADCC killer (K) cells: (Hu ⪖)Ra > Gp ⪢ Ho, Go. The data suggest that Gp IgG interacts with only a subpopulation (≈ 30%) of HuPBL K cells. The binding of aggG to total HuPBL failed to strictly correlate with the ADCC results or with the results of rosette formation between total HuPBL and CRBC-A(γ). The observations suggest that there is a heterogeneity of FcγR between K and non-K cell subpopulations of HuPBL both in terms of the type of complexed IgG they are able to bind, and in terms of the species of origin of the IgG. The data also support contentions that FcγR that bind RBCA(γ) complexes differ from those that bind aggG.