Specific activation of lymphocytes against acetylcholine receptor in the thymus in myasthenia gravis

In 13 patients with myasthenia gravis, spontaneous in vitro production of antibody to acetylcholine receptor (AChR) by thymic cells was observed in seven patients, by bone marrow cells in nine, by peripheral blood cells (PBL) in six, and by lymph node cells in nine. The rate of anti-AChR production in culture closely correlated with the serum anti-AChR level. Specific activity of the immunoglobulin (Ig) G spontaneously produced (anti-AChR/total IgG) was about 10-fold higher in the thymus than in bone marrow, peripheral blood, or lymph node cultures. Pokeweed mitogen (PWM) enhanced anti-AChR production only by PBL. With neither thymus nor lymph node cells did PWM stimulate anti-AChR production, although it greatly enhanced total IgG production. In bone marrow, it depressed both, and it appeared that the anti-AChR was derived from long-lived plasma cells that may be responsible for delaying the fall of serum anti-AChR levels after thymectomy. The results suggest that AChR-specific cells are selectively activated in the thymus, and this may help to explain the benefits of thymectomy in myasthenia gravis.