Lisak Robert P, Nedelkoska Liljana, Benjamins Joyce A, Schalk Dana, Bealmear Beverly, Touil Hanane, Li Rui, Muirhead Gillian, Bar-Or Amit
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.
J Neuroimmunol. 2017 Aug 15;309:88-99. doi: 10.1016/j.jneuroim.2017.05.004. Epub 2017 May 17.
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.
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。
