Anti-CD20 Depletes Meningeal B Cells but Does Not Halt the Formation of Meningeal Ectopic Lymphoid Tissue.

Rosa Margareta Brand, Verena Friedrich, Jolien Diddens, Monika Pfaller, Francesca Romana de Franchis, Helena Radbruch, Bernhard Hemmer, Katja Steiger, Klaus Lehmann-Horn
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引用次数: 12

Abstract

Objective: To investigate whether anti-CD20 B-cell-depleting monoclonal antibodies (ɑCD20 mAbs) inhibit the formation or retention of meningeal ectopic lymphoid tissue (mELT) in a murine model of multiple sclerosis (MS).

Methods: We used a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T-cell and B-cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in MS. ɑCD20 mAbs were administered in either a preventive or a treatment regimen. The extent and cellular composition of mELT was assessed by histology and immunohistochemistry.

Results: ɑCD20 mAb, applied in a paradigm to either prevent or treat EAE, did not alter the disease course in either condition. However, ɑCD20 mAb depleted virtually all B cells from the meningeal compartment but failed to prevent the formation of mELT altogether. Because of the absence of B cells, mELT was less densely populated with immune cells and the cellular composition was changed, with increased neutrophil granulocytes.

Conclusions: These results demonstrate that, in CNS autoimmune disease, meningeal inflammatory infiltrates may form and persist in the absence of B cells. Together with the finding that ɑCD20 mAb does not ameliorate spontaneous chronic EAE with mELT, our data suggest that mELT may have yet unknown capacities that are independent of B cells and contribute to CNS autoimmunity.

Abstract Image

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抗cd20消耗脑膜B细胞,但不能阻止脑膜异位淋巴组织的形成。
目的:探讨抗CD20 b细胞消耗单克隆抗体(CD20 mab)是否能抑制多发性硬化症(MS)小鼠脑膜异位淋巴组织(mELT)的形成或保留。方法:我们使用自发性慢性实验性自身免疫性脑脊髓炎(EAE)小鼠模型,该模型具有髓鞘少突胶质细胞糖蛋白(MOG)特异性突变t细胞和b细胞受体,其发展为类似ms中描述的脑膜炎症浸润。CD20单克隆抗体在预防或治疗方案中给予。采用组织病理学和免疫组织化学方法评估mELT的程度和细胞组成。结果:CD20单抗用于预防或治疗EAE,在两种情况下都没有改变病程。然而,CD20单抗几乎耗尽了脑膜室的所有B细胞,但未能完全阻止mELT的形成。由于缺乏B细胞,mELT的免疫细胞密度降低,细胞组成发生变化,中性粒细胞增多。结论:这些结果表明,在中枢神经系统自身免疫性疾病中,脑膜炎症浸润可能在缺乏B细胞的情况下形成并持续存在。再加上发现CD20单抗不能改善自发性慢性EAE与mELT,我们的数据表明,mELT可能具有未知的能力,不依赖于B细胞,并有助于中枢神经系统自身免疫。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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