The role of alpha7 nicotinic acetylcholine receptors in B lymphocyte activation.
The involvement of nicotinic acetylcholine receptor (nAChR) a7 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 alpha7-specific antibody and examined by flow cytometry. The alpha7-specific antibody binding interfered with that of anti-CD40 but not of anti-IgM, anti-CD16/32 or anti-CD23 suggesting that alpha7 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 alpha7 nAChR expression. Anti-CD40-induced B lymphocyte proliferation studied by [3H]thymidine incorporation was increased upon alpha7 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 alpha7 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.
Koval
L M
LM
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv. skok@biochem.kiev.ua
Yu Lykhmus
O
O
Omelchenko
D M
DM
Komisarenko
S V
SV
Skok
M V
MV
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D019013:CD40 Antigens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; C579166:Chrna7 protein, mouse; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D000157:Aconitine