Myasthenic antibodies cross-link acetylcholine receptors to accelerate degradation.
The decrease of acetylcholine receptors at neuromuscular junctions of myasthenic patients has been attributed to an antibody-mediated autoimmune process that accelerates receptor degradation. We studied the mechanism of this process in skeletal-muscle cultures, using intact antibodies and antibody fragments. Addition of myasthenic IgG or its divalent fragment, F(ab')2, to cultures accelerated the rate of acetylcholine-receptor degradation threefold. By contrast, the monovalent fragment, Fab, from myasthenic serum had no effect on degradation, although it bound to acetylcholine receptors. Addition of a second, "piggyback" antibody to cross-link the Fab:receptor complexes resulted in a threefold increase of the degradation rate. Similarly, when acetylcholine receptors with bound alpha-bungarotoxin were cross-linked by the addition of specific antibody against alpha-bungarotoxin, the degradation rate increased approximately threefold. The effect of myasthenic patients' antibodies in accelerating degradation of acetylcholine receptors is attributed to their ability to cross-link the receptors.
D001323:Autoantibodies; D002038:Bungarotoxins / Q000276:immunology; D046508:Culture Techniques; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D008954:Models, Biological; D009157:Myasthenia Gravis / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism*
D001323:Autoantibodies; D002038:Bungarotoxins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic