Clonotypic analysis of anti-acetylcholine receptor antibodies from experimental autoimmune myasthenia gravis-sensitive Lewis rats and experimental autoimmune myasthenia gravis-resistant Wistar Furth rats.
A single immunization of Lewis rats with purified acetylcholine receptor (AChR) emulsified in adjuvant typically stimulates the production of oligoclonal AChR-reactive antibodies (as demonstrated by IEF) dominated by the IgG2a subclass, of moderate but clonotypically heterogeneous relative Ag-binding avidity, and capable of inducing symptoms of experimental autoimmune myasthenia gravis. Although similar immunization of Wistar Furth rats produces AChR-reactive antibodies with similar characteristics of clonotypic heterogeneity, avidity, and isotype expression, no detectable signs of AChR-dependent muscle impairment is observed. This contrasts the ability to induce impaired AChR function upon the passive transfer of pre-formed Lewis anti-AChR antibodies into naive Wistar Furth rats, suggesting that disease resistance in this model is not conferred at the level of the AChR itself. Moreover, if more aggressive immunization protocols are used (i.e., multiple injections of AChR), a transient breakthrough of AChR-dependent muscle dysfunction can be induced directly in the Wistar Furth strain indicating that the potential for the production of disease-causing antibodies does exist in the Wistar Furth repertoire. IEF analysis of Wistar Furth anti-AChR antibodies has revealed that hyperimmunization results in modified antibody clonotype expression that might explain changing expression of disease symptoms; however, explanations for the apparent "resistance" of Wistar Furth rats to disease induction are likely to be complex.
Zoda
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Department of Microbiology, University of Texas Health Science Center, San Antonio 78284.
Yeh
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Krolick
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D000818:Animals; D000915:Antibody Affinity; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000097:blood; D007525:Isoelectric Focusing; D009119:Muscle Contraction / Q000502:physiology; D009157:Myasthenia Gravis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000502:physiology
D001323:Autoantibodies; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011950:Receptors, Cholinergic