Acetylcholine receptor-reactive antibodies in experimental autoimmune myasthenia gravis differing in disease-causing potential: subsetting of serum antibodies by preparative isoelectric focusing.
Antibodies obtained from the sera of Lewis rats demonstrating impaired neuromuscular function following immunization with purified acetylcholine receptor (AChR) were fractionated by preparative isoelectric focusing. Upon passive transfer of fractionated anti-receptor antibodies into immunologically naive, healthy recipient rats it was observed that two main subsets of AChR-specific antibody could be identified. One subset, representing about one-third of the expressed clonotypic antibody repertoire, was capable of directly perturbing AChR-dependent neuromuscular function following transfer. A second subset, demonstrated no detectable ability to induce disease symptoms following transfer. Although the anti-AChR antibodies were produced by immunization with Torpedo AChR, the inability of some antibody fractions to perturb AChR function was not explained by their inability to react with AChR of mammalian origin. Furthermore, the ability to transfer symptoms did not correspond with a particular antibody isotype (although the response was dominated by IgG2a) and did not depend solely on high relative binding avidity (benign reactivities of high relative binding avidity were also observed). Nonetheless, an anti-AChR antibody subset can be directly identified and purified from immune serum that is likely to contain reactivities that are most directly responsible for neuromuscular disease symptoms demonstrated by rats with experimental autoimmune myasthenia gravis.
Thompson
P A
PA
Department of Microbiology, University of Texas Health Science Center, San Antonio 78284.
Krolick
K A
KA
D000818:Animals; D000906:Antibodies / Q000032:analysis*; D005260:Female; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007525:Isoelectric Focusing; D009157:Myasthenia Gravis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology*
D000906:Antibodies; D007132:Immunoglobulin Isotypes; D011950:Receptors, Cholinergic