Different patterns of nicotinic acetylcholine receptor subunit transcription in human thymus

• Published in: Journal of neuroimmunology 2004-04, Vol.149 (1), p.147-159
• Main Authors: Bruno, Roxana, Sabater, Lidia, Tolosa, Eva, Sospedra, Mireia, Ferrer-Francesch, Xavier, Coll, Jaume, Foz, Marius, Melms, Arthur, Pujol-Borrell, Ricardo
• Format: Article
• Language: English
• Subjects: Acetylcholine receptor; Adolescent; Adult; Aged; Blotting, Southern - methods; Desmin - metabolism; Epithelial Cells - metabolism; Fluorescent Antibody Technique - methods; Gene Expression; Humans; Messenger RNA; Microdissection - methods; Middle Aged; Muscles - metabolism; Myasthenia gravis; Myasthenia Gravis - genetics; Myasthenia Gravis - metabolism; Protein Subunits - chemistry; Protein Subunits - genetics; Protein Subunits - metabolism; Receptors, Nicotinic - chemistry; Receptors, Nicotinic - genetics; Receptors, Nicotinic - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; RT-PCR; Thymoma - genetics; Thymoma - metabolism; Thymus; Thymus Gland - cytology; Thymus Gland - metabolism; Thymus Neoplasms - genetics; Thymus Neoplasms - metabolism; Time Factors; Tissue Distribution; Transcription, Genetic
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2003.11.022

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 ε, neonatal for γ and individually variable for α1, β1 and δ. 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 α and γ subunits.