NMDA-receptor antagonists block B-cell function but foster IL-10 production in BCR/CD40-activated B cells

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• 作者：Narasimhulu Simma ; Tanima Bose ; Sascha Kahlfu?…
• 关键词：B cell ; B10 ; Ifenprodil ; IL ; 10 ; Kv1.3 ; KCa3.1 ; LPS ; Memantine ; NMDA ; receptor antagonist
• 刊名：Cell Communication and Signaling
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：12
• 期：1
• 全文大小：5,193 KB
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• 刊物主题：Cell Biology; Protein-Ligand Interactions; Receptors; Cytokines and Growth Factors;
• 出版者：BioMed Central
• ISSN：1478-811X

文摘

Background B cells are important effectors and regulators of adaptive and innate immune responses, inflammation and autoimmunity, for instance in anti-NMDA-receptor (NMDAR) encephalitis. Thus, pharmacological modulation of B-cell function could be an effective regimen in therapeutic strategies. Since the non-competitive NMDAR antagonist memantine is clinically applied to treat advanced Alzheimer`s disease and ketamine is supposed to improve the course of resistant depression, it is important to know how these drugs affect B-cell function. Results Non-competitive NMDAR antagonists impaired B-cell receptor (BCR)- and lipopolysaccharide (LPS)-induced B-cell proliferation, reduced B-cell migration towards the chemokines SDF-1α and CCL21 and downregulated IgM and IgG secretion. Mechanistically, these effects were mediated through a blockade of Kv1.3 and KCa3.1 potassium channels and resulted in an attenuated Ca2+-flux and activation of Erk1/2, Akt and NFATc1. Interestingly, NMDAR antagonist treatment increased the frequency of IL-10 producing B cells after BCR/CD40 stimulation. Conclusions Non-competitive NMDAR antagonists attenuate BCR and Toll-like receptor 4 (TLR4) B-cell signaling and effector function and can foster IL-10 production. Consequently, NMDAR antagonists may be useful to target B cells in autoimmune diseases or pathological systemic inflammation. The drugs-additional side effects on B cells should be considered in treatments of neuronal disorders with NMDAR antagonists.