Differential involvement of α4β2, α7 and α9α10 nicotinic acetylcholine receptors in B lymphocyte activation in vitro

Lyudmyla Koval, Olena Lykhmus, Maxim Zhmak, Alexey Khruschov, Victor Tsetlin, Elena Magrini, Antonella Viola, Alexander Chernyavsky, Jing Qian, Sergei Grando, Sergei Komisarenko, Maryna Skok

Research output: Contribution to journalArticlepeer-review

Abstract

Mouse B lymphocytes express several nicotinic acetylcholine receptor (nAChR) subtypes, their exact functions being not clearly understood. Here we show that α7 nAChR was present in about 60%, while α4β2 and α9(α10) 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. α4β2 and α7, but not α9(α10) nAChRs, were up-regulated upon B lymphocyte activation in vitro. Flow cytometry and sandwich ELISA studies demonstrated that α7 and α9(α10) nAChRs are coupled to CD40, whereas α4β2 nAChR is coupled to IgM. B lymphocytes of both α7-/- and β2-/- mice responded to anti-CD40 stronger than those of the wild-type mice, whereas the cells of β2-/- mice responded to anti-IgM worse than those of the wild-type or α7-/- mice. Inhibition of α7 and α9(α10) nAChRs with methyllicaconitine resulted in considerable augmentation of CD40-mediated B lymphocyte proliferation in cells of all genotypes; stimulation of α4β2 nAChRs with epibatidine increased the IgM-mediated proliferation of the wild-type and α7-/-, but not β2-/- cells. Inhibition of α9(α10) nAChRs with α-conotoxin PeAI exerted weak stimulating effect on CD40-mediated proliferation. This nAChR subtype was up-regulated in α7-/- B-cells. α7 nAChRs were found recruited to immune synapses between human T and B lymphocytes, both of which produced acetylcholine. It is concluded that α7 nAChR fulfills inhibitory CD40-related mitogenic function, α4β2 nAChR produces a stimulatory IgM-related effect, while α9α10 nAChR is a "reserve" receptor, which partly compensates the absence of α7 nAChR in α7-/- cells. Acetylcholine is an additional mediator to modulate activation of interacting T and B lymphocytes.

Original languageEnglish
Pages (from-to)516-524
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume43
Issue number4
DOIs
Publication statusPublished - Apr 2011

Keywords

  • B lymphocytes
  • CD40
  • IgM
  • Immune synapse
  • Nicotinic acetylcholine receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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