title: The B-cell repertoire in myasthenia gravis includes all four acetylcholine receptor subunits.
abstract: By enumerating cells secreting IgG antibodies of particular specificities using an enzyme-linked immunospot (ELISPOT) assay, the B-cell responses to Torpedo acetylcholine receptor (AChR) and its alpha-, beta-, gamma- and delta-subunits in peripheral blood from patients with myasthenia gravis (MG), and controls with other neurological diseases (OND) as well as healthy subjects were determined. Compared to controls, the patients with MG had elevated numbers of B cells secreting antibodies against AChR and its alpha-, beta-, gamma- and delta-subunits in peripheral blood in parallel. The mean numbers of anti-AChR antibody secreting cells were about 17 per 10(5) blood MNC, and for the subunits 10 to 15 in MG patients, compared to between 0.8 and 1.9 per 10(5) blood MNC in OND patients, and 0.1 to 0.3 in healthy controls. Such B cells detected in controls probably represent naturally occurring B cells responded to AChR and its subunits. The finding that most (60%) MG patients had B cells predominantly recognizing the alpha-subunit may be an indirect argument for the existence of a main immunogenic region (MIR). In the remaining 40% of patients with MG the predominant B-cell responses were directed to beta-, gamma- or delta-subunit. The data suggest that all four AChR subunits may function as strong immunogens in MG, though the alpha-subunit may be the major immune target in a substantial proportion of MG patients.
authors.affiliation: Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: W Z
authors.initials: WZ
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Fredrikson
authors.forename: J
authors.initials: J
authors.lastname: Qiao
authors.forename: P O
authors.initials: PO
authors.lastname: Osterman
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D014101:Torpedo
chemical_list: D007074:Immunoglobulin G; D011950:Receptors, Cholinergic