Naor Shulamit, Keren Zohar, Bronshtein Tomer, Goren Efrat, Machluf Marcelle, Melamed Doron
Department of Immunology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
J Neurol. 2009 Aug;256(8):1228-35. doi: 10.1007/s00415-009-5097-3. Epub 2009 Mar 12.
Several recent studies proposed a role for innate immunity and inflammation in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, possible links, if any, between disease and adaptive immunity are poorly understood. The present study probed for the role of B cells in ALS disease using the G93A-SOD-1 transgenic mouse model. In agreement with other studies, we show here that autoantibodies are detectable in SOD-1 mice. However, SOD-1 B cells did not express any altered phenotype and exhibited indistinguishable responsiveness to immunogenic stimuli relative to wild-type B cells. This was obtained for B cells isolated before, during and after the onset of ALS-like disease. Finally, to obtain an in vivo conclusion, we generated SOD-1 mice that are deficient of B cells, by crossing SOD-1 mice with Igmu-deficient mice (muMT), where B cell development is blocked at the proB stage. The meteoric assays performed on a rota-rod clearly showed the development of ALS-like disease in SOD-1 mice that are deficient of B cells not differently than in control SOD-1 mice. Our results propose that B lymphocytes do not have a major role in the pathogenesis of ALS-like disease in SOD-1 mice.
最近的几项研究提出先天性免疫和炎症在肌萎缩侧索硬化症（ALS）发病机制中起作用。然而，疾病与适应性免疫之间可能存在的联系（如果有的话）却知之甚少。本研究使用G93A-SOD-1转基因小鼠模型探究B细胞在ALS疾病中的作用。与其他研究一致，我们在此表明在SOD-1小鼠中可检测到自身抗体。然而，SOD-1 B细胞未表现出任何改变的表型，并且相对于野生型B细胞，其对免疫原性刺激的反应性无明显差异。对于在ALS样疾病发作之前、期间和之后分离的B细胞均得到此结果。最后，为了得出体内结论，我们通过将SOD-1小鼠与Igmu缺陷小鼠（muMT）杂交，培育出缺乏B细胞的SOD-1小鼠，其中B细胞发育在proB阶段受阻。在旋转杆上进行的运动测定清楚地表明，缺乏B细胞的SOD-1小鼠与对照SOD-1小鼠一样，都出现了ALS样疾病的发展。我们的结果表明，B淋巴细胞在SOD-1小鼠的ALS样疾病发病机制中不起主要作用。
