title: Experimental autoimmune myasthenia gravis induction in B cell-deficient mice.
abstract: Experimental autoimmune myasthenia gravis (EAMG) is an animal model for human myasthenia gravis (MG). Autoantibody-induced functional loss of nicotinic acetylcholine receptor (AChR) at the postsynaptic membrane is an important pathogenic feature of both MG and EAMG. To evaluate the extent at which the humoral immune response against AChR operates in the pathogenesis of EAMG, we immunized B cell knockout (muMT) and wild-type C57BL/6 mice with AChR and complete Freund's adjuvant. The ability of AChR-primed lymph node cells to proliferate and secrete IFN-gamma in response to AChR and its dominant peptide alpha146-162 were intact in muMT mice as in wild-type mice. Similar amounts of mRNA for IFN-gamma, IL-4 and IL-10 in AChR-reactive lymph node cells were detected in muMT and wild-type mice. However, muMT mice had no detectable anti-AChR antibodies and remained completely free from clinical EAMG. We conclude that B cells are critically required for the genesis of clinical EAMG, but not for AChR-specific T cell priming.
authors.affiliation: Division of Neurology, Karolinska Institute, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: F D
authors.initials: FD
authors.lastname: Shi
authors.forename: B
authors.initials: B
authors.lastname: He
authors.forename: M
authors.initials: M
authors.lastname: Bakheit
authors.forename: B
authors.initials: B
authors.lastname: Wahren
authors.forename: A
authors.initials: A
authors.lastname: Berglöf
authors.forename: K
authors.initials: K
authors.lastname: Sandstedt
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009132:Muscles / Q000473:pathology; D009157:Myasthenia Gravis / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D007371:Interferon-gamma