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

Cell Communication and Signaling

Research

Fred Lühder¹  Narasimhulu Simma²  Thomas Schüler²  Ursula Bommhardt²  Theresa Lowinus²  Judith Mankiewicz²  Sascha Kahlfuß²  Burkhart Schraven³  Tanima Bose⁴  Martin Heine⁴ 

[1] Department of Neuroimmunology, Institute for Multiple Sclerosis Research and The Hertie Foundation, Waldweg 33, 37073, Göttingen, Germany;Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany;Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany;Department of Immune Control, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124, Braunschweig, Germany;RG Molecular Physiology, Leibniz Institute of Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany;

关键词: B cell;    B10;    Ifenprodil;    IL-10;    Kv1.3;    KCa3.1;    LPS;    Memantine;    NMDA-receptor antagonist;   

DOI  :  10.1186/s12964-014-0075-5

 received in 2014-04-30, accepted in 2014-11-12,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundB 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.ResultsNon-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.ConclusionsNon-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.

【 授权许可】

Unknown   
© Simma et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.