Effector mechanisms in myasthenia gravis: end-plate function after passive transfer of IgG, Fab, and F(ab')2 hybrid molecules.
Using the quantitative ionophoresis technique and the mouse passive transfer model of myasthenia gravis, end-plate function was measured in mice transferred with myasthenic IgG, 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 IgG or IgG fragments. In contrast, myasthenic IgG and Fab, but not control IgG 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 IgG or IgG 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 cross-linking of AChR by divalent antibody may not be an absolute requirement for the reduction of AChR at the functional neuromuscular synapse.
R
R
Sterz
R
R
Hohlfeld
K
K
Rajki
M
M
Kaul
K
K
Heininger
K
K
Peper
K V
KV
Toyka
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007116:Immunization, Passive; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007473:Ion Channels / Q000276:immunology; D051379:Mice; D009157:Myasthenia Gravis / Q000276:immunology*; D009469:Neuromuscular Junction / Q000276:immunology*; D055503:Protein Multimerization; D011950:Receptors, Cholinergic / Q000276:immunology; D009435:Synaptic Transmission
D001323:Autoantibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007473:Ion Channels; D011950:Receptors, Cholinergic