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

Abstract

We studied the binding of [3H]-epibatidine and [125I-]α-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 α4(α5)β2 and 3130±750 of α7(α5β4) nicotinic acetylcholine receptors per cell. According to flow cytometry data, the highest expression of α4(α5)β2 receptors was observed in immature newly generated B lymphocytes of the bone marrow, while the number of α7(α5β4) receptors grew up along with the B cell maturation in the spleen. By using α4, β2 or α7 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 α7-containing subtype only. Moreover, mature B lymphocytes became sensitive to nicotine only in the absence of β2-containing receptors. Knockout mice had less serum IgG, IgG-producing cells and natural IgG antibodies than their wild-type counterparts, while the absence of β2-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.