Antigenic modulation of junctional acetylcholine receptor is not sufficient to account for the development of myasthenia gravis in receptor immunized mice.

Myasthenia gravis (MG) is a disease thought to result from an autoimmune response against the nicotinic acetylcholine receptor of the neuromuscular junction. Although there is little doubt that the muscular weakness characteristic of MG can be attributed to an antibody-mediated reduction in the density of AChR, the mechanism responsible for this reduction remains uncertain. In the present studies we have used a mouse model of MG, termed experimental myasthenia gravis (EMG), to test the possibility that antigenic modulation of AChR may be the principle mechanism whereby this reduction in AChR density is achieved. We found that immunization of mice with AChR, on average, leads to a twofold increase in the rate of junctional AChR degradation. Because this effect occurred to the same extent in mice that developed severe paralysis and in those that gave no indication of muscular weakness, the role of antigenic modulation as a major pathologic mechanism in MG is questioned.