Nicotinic receptors regulate B lymphocyte activation and immune response.
The presence of nicotinic acetylcholine receptors (nicotinic receptors) composed of either alpha7 or alpha4 and beta2 subunits is revealed in B lymphocytes by means of radioligand binding assay and Cell ELISA. Mouse B lymphocytes contained 12,200+/-3200 of epibatidine-binding sites and 3130+/-750 of alpha-Bungarotoxin-binding sites per cell. Mice lacking nicotinic receptor subunits alpha4, beta2 or alpha7 had less serum IgG and IgG-producing cells in the spleen, but showed stronger immune response to both protein antigen in vivo and CD40-specific antibody in vitro than wild-type mice. Anti-CD40-stimulated proliferation of B lymphocytes from beta2 knockout, but not wild-type mice was inhibited with nicotine. Our results indicate that signalling through nicotinic receptors affects both the pre-immune state and activation of B lymphocytes in the immune response, possibly via CD40-dependent pathway. This could contribute to immune depression found in tobacco smokers.
Skok
Marina
M
Department of Molecular Immunology, Palladin Institute of Biochemistry, 9, Leontovicha str., 01601 Kyiv, Ukraine. skok@biochem.kiev.ua
Grailhe
Régis
R
Changeux
Jean-Pierre
JP
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002038:Bungarotoxins / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood*; D007457:Iodine Radioisotopes; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011725:Pyridines / Q000378:metabolism; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014316:Tritium
D000906:Antibodies; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D019013:CD40 Antigens; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D021122:Protein Subunits; D011725:Pyridines; D011978:Receptors, Nicotinic; D014316:Tritium; C082748:epibatidine