Differential expression of nicotinic acetylcholine receptor subunits in fetal and neonatal mouse thymus

Studies were initiated to identify nicotinic acetylcholine receptor (nAChR) subunits and subtypes expressed in the developing immune system and cell types on which nAChR are expressed. Reported here are reverse transcription-polymerase chain reactions (RT-PCR) studies of nAChR alpha2-alpha7 and beta2-beta4 subunit gene expression using fetal or neonatal regular or scid/scid C57BL/6 mouse thymus. Findings are augmented with studies of murine fetal thymic organ cultures (FOTC) and of human peripheral lymphocytes. Novel partial cDNA sequences were derived for mouse nAChR alpha2, alpha3, beta3 and beta4 subunits, polymorphisms were identified in mouse nAChR alpha4, alpha7 and beta2 subunits, and recently derived sequences for mouse nAChR alpha5 and alpha6 subunits were confirmed. Thymic stromal cells appear to express nAChR alpha2, alpha3, alpha4, alpha7 and beta4 subunits, perhaps in addition to alpha5 and beta2 subunits, in a pattern reminiscent of expression in the developing brain. Immature T cells appear to express alpha3, alpha5, alpha7, beta2 and beta4 subunits, just as do neural crest-derived cells targeted by cholinergic innervation. Peripheral T cells seem to express an unusual profile of alpha2, alpha5 and alpha7 subunits, perhaps indicating that their nAChR express yet-to-be-identified assembly partners or that T cell nicotinic responsiveness occurs through homomeric nAChR composed of alpha7 subunits. Our findings are consistent with published work but show a much wider array of nAChR subunit gene expression in mouse thymic stromal and/or lymphoid cells and evidence for developmental regulation of nAChR subunit expression. These studies suggest important roles for nAChR in immune system development and function and in the neuroimmune network.