B cell autoimmunity to acetylcholine receptor and its subunits in Lewis rats over the course of experimental autoimmune myasthenia gravis.
Experimental autoimmune myasthenia gravis (EAMG) is induced by a single injection of acetylcholine receptor (AChR) with complete Freund's adjuvant and represents a useful animal model for studying the mechanisms by which autoimmune responses to AChR and its subunits are coupled to the development of human myasthenia gravis. Using an immunospot assay, we enumerated cells secreting IgG antibodies against Torpedo AChR and the alpha-, beta-, gamma- and delta-subunits of Torpedo AChR in lymph nodes, spleen and thymus from Lewis rats over the course of EAMG. Cells secreting IgG antibodies to AChR and to all four subunits were detected at higher numbers in the three immune organs in EAMG compared to controls. Numbers were highest in lymph nodes followed by spleen and thymus. Cells secreting IgG antibodies against native AChR were always higher than those against individual subunits. The immunogenicity between the four subunits did not differ, with the exception that the alpha-subunit induced a slightly higher B cell response in thymus and lymph nodes. The patterns of B cell responses were similar when analyzed over the course of EAMG from week 2 to week 5, and there was no restriction of the B cell repertoire early in EAMG. Anti-AChR and anti-subunit antibody-secreting cells were also detected in control animals immunized with adjuvant only, but at numbers which were much lower, and which were within the same level as numbers of cells secreting IgG antibodies to the control antigen myelin basic protein, probably reflecting naturally occurring autoimmune B cells.
Wang
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ZY
Department of Neurology, Karolinska Institutet, Huddinge Hospital, Stockholm, Sweden.
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Qiao
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Olsson
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Huang
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D000818:Animals; D000906:Antibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology*; D011863:Radioimmunoassay; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000145:classification / Q000276:immunology*; D014101:Torpedo
D000906:Antibodies; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic