来自多发性硬化症患者的B细胞在体外通过凋亡诱导神经元细胞死亡。

B cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro.

作者信息

Lisak Robert P, Nedelkoska Liljana, Benjamins Joyce A, Schalk Dana, Bealmear Beverly, Touil Hanane, Li Rui, Muirhead Gillian, Bar-Or Amit

机构信息

Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Microbiology, Immunology and Biochemistry, Wayne State University School of Medicine, Detroit, MI, USA.

Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA.

出版信息

J Neuroimmunol. 2017 Aug 15;309:88-99. doi: 10.1016/j.jneuroim.2017.05.004. Epub 2017 May 17.

DOI:10.1016/j.jneuroim.2017.05.004

PMID:28601295

Abstract

B cells mediate multiple sclerosis (MS) pathogenesis by mechanisms unrelated to immunoglobulin (Ig). We reported that supernatants (Sup) from cultured B cells from blood of relapsing remitting MS (RRMS) patients, but not normal controls (NC), were cytotoxic to rat oligodendrocytes (OL). We now show that RRMS blood B cells, not stimulated in vitro, secrete factor/s toxic to rat and human neurons. Cytotoxicity is independent of Ig and multiple cytokines, not complement-mediated, and involves apoptosis. The factor/s have an apparent mw of >300kDa. B cells could contribute to damage within the central nervous system by secreting molecules toxic to OL and neurons.

摘要

B细胞通过与免疫球蛋白（Ig）无关的机制介导多发性硬化症（MS）的发病机制。我们报道，复发缓解型MS（RRMS）患者血液中培养的B细胞的上清液（Sup）对大鼠少突胶质细胞（OL）具有细胞毒性，而正常对照（NC）的上清液则无此作用。我们现在发现，未经体外刺激的RRMS血液B细胞会分泌对大鼠和人类神经元有毒的因子。细胞毒性独立于Ig和多种细胞因子，不是补体介导的，并且涉及细胞凋亡。这些因子的表观分子量>300kDa。B细胞可能通过分泌对OL和神经元有毒的分子而导致中枢神经系统内的损伤。