Different patterns of nicotinic acetylcholine receptor subunit transcription in human thymus.
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.
Bruno
Roxana
R
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.
Sabater
Lidia
L
Tolosa
Eva
E
Sospedra
Mireia
M
Ferrer-Francesch
Xavier
X
Coll
Jaume
J
Foz
Marius
M
Melms
Arthur
A
Pujol-Borrell
Ricardo
R
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
D003893:Desmin; D021122:Protein Subunits; D012333:RNA, Messenger; D011978:Receptors, Nicotinic