Effector mechanisms in myasthenia gravis: End‐plate function after passive transfer of IgG, Fab, and F(ab′)2 hybrid molecules

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Abstract
Using the quantitative ionophoresis technique and the mouse passive transfer model of myasthenia gravis, end-plate function was measured in mice transferred with myasthenic lgG, Fab, or F(ab')2 hybrid molecules prepared by recombination of one acetylcholine receptor (AChR) specific Fab and one Fab directed against irrelevant antigen. The Hill coefficient (a measure for the cooperativity between AChR subunits) and the apparent dissociation constant K for the ACh-AChR interaction were essentially unaltered after passive transfer of lgG or lgG fragments. In contrast, myasthenic lgG and Fab, but not control lgG or Fab, markedly reduced the mean number of end-plate channels. A similar effect was observed after passive transfer of F(ab')2 hybrid molecules. These results show that passive transfer of myasthenic lgG or lgG fragments leads to a quantitative reduction of ACh-controlled end-plate channels, whereas the function of the remaining receptors/channels remains unchanged. The results suggest further that crosslinking of AChR by divalent antibody may not be an absolute requirement for the reduction of AChR at the functional neuromuscular synapse.