Co-cross-linking of surface immunoglobulin Fc gamma receptors on B lymphocytes uncouples the antigen receptors from their associated G protein.
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 Fc gamma 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) (GTP gamma S), but not the basal stimulation of Gp induced by GTP gamma S alone. These results therefore indicate that co-cross-linkage of sIg and Fc gamma 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.
Rigley
K P
KP
Division of Immunology, National Institute for Medical Research, Mill Hill, London, GB.
Harnett
M M
MM
Klaus
G G
GG
D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D019204:GTP-Binding Proteins / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000032:analysis; D011946:Receptors, Antigen / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG
D000943:Antigens, Differentiation; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011946:Receptors, Antigen; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG; D010727:Phosphoric Diester Hydrolases; D019204:GTP-Binding Proteins