Resistance to experimental autoimmune myasthenia gravis in IL-6-deficient mice is associated with reduced germinal center formation and C3 production.
To provide direct genetic evidence for a role of IL-6 in experimental autoimmune myasthenia gravis (EAMG), IL-6 gene KO (IL-6(-/-)) mice in the C57BL/6 background were immunized with Torpedo californica acetylcholine receptor (AChR) and evaluated for EAMG. Only 25% of AChR-immunized IL-6(-/-) mice developed clinical EAMG compared to 83% of C57BL/6 (wild-type) mice. A significant reduction in the secondary anti-AChR Ab of IgG, IgG(2b), and IgG(2c), but not the primary or secondary IgM response was observed in AChR-immunized IL-6(-/-) mice, suggesting a possible defect in T cell help and class switching to anti-AChR IgG(2) isotype. The AChR-specific lymphocyte proliferative response, IFN-gamma, and IL-10 production were suppressed in AChR-immunized IL-6(-/-) mice. EAMG resistance in IL-6(-/-) mice was associated with a significant reduction in germinal center formation and decreased serum complement C3 levels. The data provide the first direct genetic evidence for a key role of IL-6 in the autoimmune response to AChR and in EAMG pathogenesis.
Deng
Caishu
C
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Goluszko
Elzbieta
E
Tüzün
Erdem
E
Yang
Huan
H
Christadoss
Premkumar
P
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D003176:Complement C3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D017099:IgG Deficiency / Q000235:genetics; D007111:Immunity, Cellular / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007117:Immunization, Secondary; D016056:Immunodominant Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D011950:Receptors, Cholinergic / Q000008:administration & dosage / Q000276:immunology
D001323:Autoantibodies; D015415:Biomarkers; D003176:Complement C3; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D015850:Interleukin-6; D010446:Peptide Fragments; D011950:Receptors, Cholinergic