Acetylcholine receptor antibody synthesis in lymphocyte cultures

The synthesis of immunoglobulin and acetylcholine receptor antibody by lymphocytes extracted from the peripheral blood and thymus of patients with myasthenia gravis was investigated using the Marbrook culture system. Small amounts of immunoglobulin were synthesised by thymic lymphocytes cultured in medium without mitogen for 14 days and acetylcholine receptor antibody activity was detectable in cultures from 3 out of 5 patients with thymic hyperplasia. Addition of Pokeweed mitogen to the cultures increased both IgG and acetylcholine receptor antibody synthesis and under these conditions receptor antibody activity was detectable in all 5 thymic lymphocyte cultures studied. Peripheral blood lymphocytes also produced small amounts of IgG when cultured in the absence of mitogen but acetylcholine receptor antibody levels were undetectable. In the presence of Pokeweed mitogen, however, peripheral blood lymphocytes synthesised increased amounts of IgG and acetylcholine receptor antibody activity was detectable in cultures of lymphocytes from 3 out of 4 patients. The amount of acetylcholine receptor antibody per microgram IgG, the specific activity, was greater in cultures of thymic lymphocytes than the specific activity of IgG in serum, suggesting that the hyperplastic thymus may be a major site of acetylcholine receptor antibody synthesis. Therefore it should be possible to use the culture system described to investigate the processes involved in the breakdown of self-tolerance in myasthenia gravis.