THE ROLE OF 7 NICOTINIC ACETYLCHOLINE RECEPTORS IN B LYMPHOCYTE ACTIVATION
L. M. Koval, O. Yu. Lykhmus, D. M. Omelchenko, S. V. Komisarenko, M. V. Skok
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
The involvement of nicotinic acetylcholine receptor (nAChR) ?7 subtype in B lymphocyte activation has been investigated. B lymphocytes were magnetically separated from the spleens of C57Bl/6J mice. The purified lymphocytes were treated with fluorescently labeled IgM-, CD40- , CD16/32 or CD23-specific antibodies and unlabeled ?7-specific antibody and examined by flow cytometry. The ?7-specific antibody binding interfered with that of anti-CD40 but not of anti-IgM, anti-CD16/32 or anti-CD23 suggesting that ?7 nAChRs are located close to CD40. B lymphocyte activation either in vitro with anti-CD40 or in vivo by immunization with cytochrome c resulted in increased ?7 nAChR expression. Anti-CD40-induced B lymphocyte proliferation studied by [3H]thymidine incorporation was increased upon ?7 nAChR inhibition with methyllicaconitine, choline or antibiotic gentamicin, as well as in the presence of the inhibitor of acetylcholine synthesis hemicholine-3. Mice injected with both cytochrome c and methyllicaconitine responded with IgM anti-cytochrome c antibodies faster than those injected with cytochrome c alone, while the secondary IgG responses were similar. It is concluded that ?7 nAChRs negatively control CD40-mediated B lymphocyte proliferation but did not affect the IgM-IgG class switch or memory B cell activation. Endogenous acetylcholine may be regarded as an auto/paracrine regulator of B lymphocyte activation.
Key words: nicotinic acetylcholine receptot, B lymphocytes, CD40, lymphocyte activation.
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