Inhibitory IgG receptor FcgammaRIIB fails to inhibit experimental autoimmune myasthenia gravis pathogenesis.
Deficiency of the inhibitory FcgammaRIIB renders mice susceptible to autoimmune disorders characterized with cellular infiltration of target tissue. To analyze the role of FcgammaRIIB in an antibody-mediated autoimmune disease, experimental autoimmune myasthenia gravis (EAMG), FcgammaRIIB knockout (KO) and wild-type mice were immunized with acetylcholine receptor (AChR). In contrast with previous reports, FcgammaRIIB KO mice were mildly resistant to EAMG despite preserved anti-AChR antibody production and neuromuscular junction complement deposition capacity. EAMG resistance was associated with reduced lymph node cell IL-6 and IL-10 production and increased CD4(+)CD25(+) cell ratios in lymph nodes. Our data suggest that FcgammaRIIB promotes antibody-mediated autoimmunity.
Li
Jing
J
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555-1070, USA.
Tüzün
Erdem
E
Wu
Xiong Rong
XR
Qi
Hui Bin
HB
Allman
Windy
W
Saini
Shamsher S
SS
Christadoss
Premkumar
P
D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood; D001323:Autoantibodies / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003176:Complement C3 / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D020022:Genetic Predisposition to Disease; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D016207:Cytokines; C499172:Fcgr2b protein, mouse; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011950:Receptors, Cholinergic; D017452:Receptors, IgG