Complement regulator CD59 deficiency fails to augment susceptibility to actively induced experimental autoimmune myasthenia gravis.
Complement deficient mice are resistant to experimental autoimmune myasthenia gravis (EAMG), suggesting a pivotal role for the membrane attack complex (MAC) in EAMG pathogenesis. To test the significance of MAC regulation in EAMG pathogenesis, CD59 KO and wild type mice were immunized with acetylcholine receptor (AChR). Interestingly, deletion of CD59, the regulator of MAC assembly, failed to augment EAMG susceptibility. The CD59 KO mice had reduced serum anti-AChR IgG1, IgG2b and complement levels. Their lymph node cell IL-2 production and lymphocyte proliferation response to AChR were reduced. The data challenge the current paradigm that CD59 is solely involved in MAC regulation and suggest a role for this molecule in antigen-driven T cell and B cell activation.
Tüzün
Erdem
E
Department of Microbiology and Immunology, The University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1070, USA.
Saini
Shamsher S
SS
Morgan
B Paul
BP
Christadoss
Premkumar
P
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D018957:CD59 Antigens / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D004198:Disease Susceptibility / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014101:Torpedo
D018957:CD59 Antigens; D003176:Complement C3; D003181:Complement C4; D015938:Complement Membrane Attack Complex; D007074:Immunoglobulin G; D007376:Interleukin-2; D021122:Protein Subunits; D011950:Receptors, Cholinergic