title: Different patterns of nicotinic acetylcholine receptor subunit transcription in human thymus.
abstract: Clinical observations suggest that the thymus is strongly implicated in the pathogenesis of myasthenia gravis (MG), but questions such as the level and location of nicotinic acetylcholine receptor (AChR) subunit expression that are fundamental to postulate any pathogenic mechanism, remain controversial. We have re-examined this question by combining calibrated RT-PCR and real-time PCR to study nicotinic AChR subunit mRNA expression in a panel of normal and myasthenic thymi. The results suggest that the expression of the different AChR subunits follows three distinct patterns: constitutive for, neonatal for gamma and individually variable for alpha1, beta1 and delta. Experiments using confocal laser microdissection suggest that AChR is mainly expressed in the medullary compartment of the thymus but there is not a clear compartmentalization of subunit expression. The different patterns of subunit expression may influence decisively the level of central tolerance to the subunits and explain the focusing of the T cell response to the alpha and gamma subunits.
authors.affiliation: Reference Health Services-Center for Transfusion and Tissue Bank, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Hospital Universitari Germans Trias i Pujol, Spain.
authors.forename: Roxana
authors.initials: R
authors.lastname: Bruno
authors.forename: Lidia
authors.initials: L
authors.lastname: Sabater
authors.forename: Eva
authors.initials: E
authors.lastname: Tolosa
authors.forename: Mireia
authors.initials: M
authors.lastname: Sospedra
authors.forename: Xavier
authors.initials: X
authors.lastname: Ferrer-Francesch
authors.forename: Jaume
authors.initials: J
authors.lastname: Coll
authors.forename: Marius
authors.initials: M
authors.lastname: Foz
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pujol-Borrell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015139:Blotting, Southern / Q000379:methods; D003893:Desmin / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005455:Fluorescent Antibody Technique / Q000379:methods; D015870:Gene Expression; D006801:Humans; D042282:Microdissection / Q000379:methods; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D009157:Myasthenia Gravis / Q000235:genetics* / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013945:Thymoma / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: D003893:Desmin; D021122:Protein Subunits; D012333:RNA, Messenger; D011978:Receptors, Nicotinic