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标题：Muscarinic Acetylcholine Receptors Modulate Interleukin-6 Production and Immunoglobulin Class Switching in Daudi Cells
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作者：Masato Mashimo ; Marina Fujii ; Natsumi Sakagawa 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2020
卷号：43
期号：12
页码：1950-1953
DOI：10.1248/bpb.b20-00461
出版社：The Pharmaceutical Society of Japan
摘要：B cells express muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs, respectively). Following immunization with ovalbumin, serum immunoglobulin G (IgG) and interleukin (IL)-6 levels were lower in M 1 and M 5 mAChR double-deficient mice and higher in α7 nAChR-deficient mice than in wild-type mice. This suggests mAChRs participate in the cytokine production involved in B cell differentiation into plasma cells, which induces immunoglobulin class switching from IgM to IgG. However, because these results were obtained with conventional knockout mice, in which all cells in the body were affected, the specific roles of these receptors expressed in B cells remains unclear. In the present study, Daudi B lymphoblast cells were used to investigate the specific roles of mAChRs and nAChR in B cells. Stimulating Daudi cells using Pansorbin cells (heat-killed, formalin-fixed Staphylococcus aureus coated with protein A) upregulated expression of M 1 –M 4 mAChRs and the α4 nAChR subunit. Under these conditions, mAChRs, but not nAChRs, mediated immunoglobulin class switching to IgG. This effect was blocked by scopolamine, a non-selective mAChR antagonist, and 4-diphenylacetoxy- N -methyl-piperidine methiodide (4-DAMP), a G q/11 -coupled M 1 , M 3 , M 5 antagonist. In addition, IL-6 secretion was further enhanced following mAChR activation. Thus, G q/11 -coupled mAChRs expressed in B cells thus appear to contribute to IL-6 production and B cell maturation into IgG-producing plasma cells.
关键词：muscarinic acetylcholine receptor;B cell;immunoglobulin class switching;interleukin-6