Koval_2011_Int.J.Biochem.Cell.Biol_43_516

Mouse B lymphocytes express several nicotinic acetylcholine receptor (nAChR) subtypes, their exact functions being not clearly understood. Here we show that alpha7 nAChR was present in about 60%, while alpha4beta2 and alpha9(alpha10) nAChRs in about 10% and 20% of mouse spleen B lymphocytes, respectively; Balb/c and C57Bl/6 mice possessed different relative amounts of these nAChR subtypes. alpha4beta2 and alpha7, but not alpha9(alpha10) nAChRs, were up-regulated upon B lymphocyte activation in vitro. Flow cytometry and sandwich ELISA studies demonstrated that alpha7 and alpha9(alpha10) nAChRs are coupled to CD40, whereas alpha4beta2 nAChR is coupled to IgM. B lymphocytes of both alpha7(-/-) and beta2(-/-) mice responded to anti-CD40 stronger than those of the wild-type mice, whereas the cells of beta2(-/-) mice responded to anti-IgM worse than those of the wild-type or alpha7(-/-) mice. Inhibition of alpha7 and alpha9(alpha10) nAChRs with methyllicaconitine resulted in considerable augmentation of CD40-mediated B lymphocyte proliferation in cells of all genotypes; stimulation of alpha4beta2 nAChRs with epibatidine increased the IgM-mediated proliferation of the wild-type and alpha7(-/-), but not beta2(-/-) cells. Inhibition of alpha9(alpha10) nAChRs with alpha-conotoxin PeAI exerted weak stimulating effect on CD40-mediated proliferation. This nAChR subtype was up-regulated in alpha7(-/-) B-cells. alpha7 nAChRs were found recruited to immune synapses between human T and B lymphocytes, both of which produced acetylcholine. It is concluded that alpha7 nAChR fulfills inhibitory CD40-related mitogenic function, alpha4beta2 nAChR produces a stimulatory IgM-related effect, while alpha9alpha10 nAChR is a "reserve" receptor, which partly compensates the absence of alpha7 nAChR in alpha7(-/-) cells. Acetylcholine is an additional mediator to modulate activation of interacting T and B lymphocytes.