Antibody bipolar bridging: Isotype-dependent signals given to guinea pig alveolar macrophages by anti-MHC alloantibodies

Abstract

Antibody bipolar bridging of a cell membrane is the phenomenon by which an antibody specifically binds to the corresponding membrane antigen through its Fab and concomitantly to a membrane Fc receptor, through its Fc, thus forming a molecular bridge at the cell surface. This phenomenon, already described on mouse mast cells with anti-H-2 IgG1 antibodies and on guinea pig polymorphonuclear leukocytes with anti-GPLA IgG2 antibodies, presently is extended to and studied on guinea pig alveolar macrophages. These cell membranes present class I and class II MHC (GPLA) antigens as demonstrated by protein-A-sheep red blood cell resetting and ELISA techniques. They also present Fc receptors for IgG2 and IgG1 as shown by an ELISA technique. IgG2 antibodies (but not their F(Ab′) 2) directed against corresponding class I or class II antigens induce a positive signal on alveolar macrophages, leading them to release H 2O 2 and superoxide anions as detected by a burst of chemiluminescence. This respiratory burst begins almost immediately, peaks at 4 to 11 min (depending on antibody concentrations), and decreases thereafter. There is a striking dose-effect curve. By contrast, IgG1 antibodies (but not there F(ab′) 2) induce a negative signal leading to a decrease of the background chemiluminescence. This type of mechanism appears potentially to be of importance in immune regulation.