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 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. © 2004 Elsevier B.V. All rights reserved.