The role of nicotinic receptors in B-lymphocyte development and activation

We studied the binding of [H-3]-epibatidine and [I-125-]alpha-bungarotoxin, as well as subunit-specific antibodies with purified B lymphocytes of C57B1/6J mice and found that these cells contained 12,200 +/- 3200 of alpha 4(alpha 5)beta 2 and 3130 +/- 750 of alpha 7(alpha 5 beta 4) nicotinic acetylcholine receptors per cell. According to flow cytometry data, the highest expression of alpha 4(alpha 5)beta 2 receptors was observed in immature newly generated B lymphocytes of the bone marrow, while the number of alpha 7(alpha 5 beta 4) receptors grew up along with the B cell maturation in the spleen. By using alpha 4, beta 2 or alpha 7 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 alpha 7-containing subtype only. Moreover, mature B lymphocytes became sensitive to nicotine only in the absence of beta 2-containing receptors. Knockout mice had less serum IgG, IgG-producing cells and natural IgG antibodies than their wild-type counterparts, while the absence of beta 2-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. (c) 2007 Elsevier Inc. All rights reserved.