Study of two different subpopulations of anti-acetylcholine receptor antibodies in a rabbit with experimental auto-immune myasthenia gravis

Two different subpopulations of anti-acetylcholine receptor antibodies were studied during the evolution of experimental autoimmune myasthenia in one rabbit immunized with Torpedo acetylcholine receptor. The results show that the subpopulation of antibodies directed against the toxin-binding site of the receptor might play a role in the appearance of the paralysis observed in this particular case

Accessibility to antibodies of acetylcholine receptors in the neuromuscular junction

Antibodies to the acetylcholine receptor are present in the serum of myasthenic patients but one does not know if, in vivo and in situ, they can penetrate the intact neuromuscular junction and block directly the receptor. The present experiments demonstrate that molecules the size of antibodies can reach acetylcholine receptor in situ. The mouse diaphragm with its intact neuromuscular junction was used as a source of acetylcholine receptor. The receptor was revealed either directly by iodinated alpha-bungarotoxin covalently coupled to IgG or indirectly, once labelled with cobra toxin, by iodinated anti-cobra toxin antibodies

Experimental myasthenia in Balb/c mice immunized with rat acetylcholine receptor from rat denervated muscle.

A new model of an autoimmune disease of the neuromuscular junction was obtained by injection of acetylcholine receptor purified from rat denervated muscles into Balb/c mice. Anti-rat, then anti-mouse acetylcholine receptor antibodies, appear in mouse serum during the immunization procedure. Electrophysiological investigations performed on immunized mice reveal a neuromuscular block similar to that found in myasthenia gravis. Not a single mouse with objective signs of muscular weakness was lacking anti-mouse acetylcholine receptor antibodies but no correlation was found between their level and the severity of the disease

Intrathymic pathogenesis of myasthenia gravis: transient expression of acetylcholine receptors on thymus-derived myogenic cells

Differentiation of myogenic stem cells from undifferentiated thymic stem cells is thought to play a critical role in the pathogenesis of myasthenia gravis. The expression of membrane acetylcholine receptor (AChR) on the membranes of developing muscle clones in cultures of murine thymus reticulum was followed and found to be transient. AChR are first expressed shortly after fusion of myotubes. In subsequent stages of myogenic development, the density of homogenously distributed AChR is strongly increased, and, in addition, concentrated "hot spot" AChR areas appear. During further maturation, membrane AChR are lost. Highly mature myotubes (3 months in culture) lack substantial amounts of homogenous AChR, as well as hot spots