CD19+CD24highCD38high调节性B细胞在视神经脊髓炎自身免疫机制中的作用

视神经脊髓炎（NMO）以反复发作的视神经和脊髓的自身免疫性炎症为特征，致残率高，治疗措施有限。NMO-IgG的发现提示B细胞在NMO发病机制中作用关键。研究表明，除了促进自身免疫反应，部分B细胞可通过表达IL-10起免疫调节作用，称调节性B细胞（Breg）。Breg因其特性可能对NMO具潜在的治疗作用，但有关NMO患者的Breg功能研究尚少。我们的前期实验证明：NMO外周血CD19+CD24highCD38highBreg的数量及B细胞IL-10的表达水平均显著降低，这种变化在NMO-IgG阳性的患者中更为突出。为此，我们将以Breg为切入点，进一步研究NMO外周血Breg与记忆性B细胞（Bm）之间免疫平衡状态的变化；探索Breg对Bm、CD4+T细胞的作用和作用途径；并利用体外组织培养NMO模型这一全新工具，研究Breg在NMO病理损害形成过程中的作用。以期为B细胞靶向治疗提供重要依据。

Neuromyelitis optica (NMO) is an autoimmun disease of the central nervous system characterized by recurrent attacks of optic neuritis and longitudinally extended transverse myelitis. NMO is an important cause of disability with limited therapeutic strategy. The discovery of NMO-IgG has indicated that B cells may play a key role in the pathogenesis of NMO.Besides promoting the autoimmun reaction, some B cell subsets may exhibit immuno-regulatory capacities through producing IL-10.These B cells are named regulatory B cells(Bregs)and may have potential therapeutic effects in NMO,but the role of Bregs in NMO pathogenesis is seldom investigated. Our previous study demonstrated that CD19+CD24highCD38high Breg of NMO was numerically difficient and B cells of NMO patients produced less IL-10.The suppressive immuno-regulatory function of B cells in NMO-IgG positive NMO patients was even more seriously impaired than that in NMO-IgG negative NMO patients.In the present study, we will focus on Bregs and further investigate the immuno-balance status between Bregs and memory B cells (Bms); the impact of Bregs on CD4+ T cell functions and the possible pathways. Meanwhile, we will establish the ex vivo spinal cord slice model of NMO using wild type mice to investigate the impact of Bregs on the spinal cord lesion severity.In conclusion, we aim to explore the functions of Bregs of NMO patients systematically in order to provide a theoretical basis for B cells as a target for immuno-therapy in NMO.