Co‐cross‐linking of surface immunoglobulin Fcγ receptors on B lymphocytes uncouples the antigen receptors from their associated G protein

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Abstract
Cross-linking of surface Ig receptors (sIg) by mitogenic forms of anti-Ig antibodies (e.g. F(ab′)2 fragments of rabbit anti-Ig) causes the rapid, and prolonged breakdown of phosphatidylinositol 4,5-bisphosphate. This response involves an unidentified guanine nucleotide regulatory protein (termed Gp), which couples sIg to the polyphosphoinositide-specific phosphodiesterase. Intact (IgG) rabbit anti-Ig antibodies, which co-cross-link sIg and Fcγ receptors on B cells, only induce short-lived inositol phospholipid breakdown and abortive B cell activation. We show here that in permeabilized B cells intact anti-Ig inhibits the reconstituted breakdown of inositol phospholipids given by a combination of F(ab′)2 anti-Ig and the non-hydrolyzable GTP analogue guanosine-5′-O-(3-thiotriphosphate) (GTPγS), but not the basal stimulation of Gp induced by GTPγS alone. These results therefore indicate that cocross-linkage of sIg and Fcγ receptors on B cells uncouples the antigen receptors from the associated G protein, but does not affect coupling between Gp and the phosphodiesterase. These observations therefore provide further insight into the mechanisms whereby engaging Fc receptors on B cells, by antigen-antibody complexes for example, could modulate antigen-induced B cell activation.