The role of nicotinic receptors in B-lymphocyte development and activation.
We studied the binding of [(3)H]-epibatidine and [(125)I-]alpha-bungarotoxin, as well as subunit-specific antibodies with purified B lymphocytes of C57Bl/6J mice and found that these cells contained 12,200+/-3200 of alpha4(alpha5)beta2 and 3130+/-750 of alpha7(alpha5beta4) nicotinic acetylcholine receptors per cell. According to flow cytometry data, the highest expression of alpha4(alpha5)beta2 receptors was observed in immature newly generated B lymphocytes of the bone marrow, while the number of alpha7(alpha5beta4) receptors grew up along with the B cell maturation in the spleen. By using alpha4, beta2 or alpha7 knockout and chimera mice, it was shown that both receptor subtypes supported the survival of B cell precursors and increased the size of B-lymphocyte population in the bone marrow. In contrast, propagation of mature B lymphocytes in the spleen was controlled by alpha7-containing subtype only. Moreover, mature B lymphocytes became sensitive to nicotine only in the absence of beta2-containing receptors. Knockout mice had less serum IgG, IgG-producing cells and natural IgG antibodies than their wild-type counterparts, while the absence of beta2-containing receptors resulted in increased B-lymphocyte activation and antibody immune response. The data obtained indicate that nicotinic receptors are involved in regulating B-lymphocyte development and activation, possibly, by affecting expression and/or signaling of CD40, the two subtypes playing different roles.
Skok
M V
MV
Palladin Institute of Biochemistry, 9, Leontovicha str., 01601 Kiev, Ukraine. skok@biochem.kiev.ua
Grailhe
R
R
Agenes
F
F
Changeux
J-P
JP
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D001667:Binding, Competitive; D008213:Lymphocyte Activation; D051379:Mice; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
D000906:Antibodies; D021122:Protein Subunits; D011978:Receptors, Nicotinic