Abstract
Immunization of groups of rats with 0.1โ100 ฮผg of acetylcholine receptor (AChR) purified from the electric organ of Torpedo californica resulted in doseโdependent (1) loss of acetylcholine receptor from the rats' muscles, (2) binding of antibodies to many of the receptors remaining in muscle, and (3) production of antibodies in serum capable of crossโreacting with receptor solubilized from rat muscle. Addition of antibodies from rats immunized with electric organ acetylcholine receptors to muscle cells in culture caused loss of receptor by accelerating the rate of receptor degradation. Monovalent antibody fragments did not accelerate degradation unless antiantibody was added to crossโlink the monovalent antibody fragments bound to receptors. This indicates that crossโlinking of receptors by antibody molecules triggers accelerated receptor degradation, leading to receptor loss. The rate of increase in receptor destruction due to antigenic modulation observed in vitro appears sufficient to account for the extent of receptor loss observed in vivo. Endocytosis of antibody crossโlinked receptors may be a rateโlimiting step common to antigenic modulation in vitro and in vivo.