在CVID患者中的抗体分泌能力:免疫球蛋白同型和抗原特异性在T细胞依赖的体外刺激后
Sophie Steiner1, Kirsten Wittke1, Sandra Bauer1
1Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
常见变性免疫缺陷 (CVID) 患者的记忆B细胞可以在体外分化为抗体分泌细胞,但IgA分泌仍然受损. 这表明,量身定制的疗法有可能在CVID中恢复B细胞功能.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 传染性疾病 传染性疾病
背景情况:
- 常见变性免疫缺陷 (CVID) 是一种主要免疫缺陷,其特征是B细胞分化和抗体产生受损.
- 冠状病毒导致复发性感染,需要终身免疫球蛋白替代疗法.
- 了解CVID中B细胞缺陷对于开发向治疗至关重要.
研究的目的:
- 在CVID患者中,研究记忆B细胞 (MBCs) 进入抗体分泌细胞 (ASCs) 的体外分化能力.
- 为了比较不同的B细胞分化的体外刺激方案的疗效.
- 评估在CVID中恢复功能B细胞反应的潜力.
主要方法:
- 来自CVID患者和健康对照者的外周血液单核细胞使用两个不同的协议来刺激.
- 议定书I:金黄色葡萄球菌 考恩菌株I,Pokeweed菌原体和CpG.
- 协议II:使用CD40连接体,白内素-21和CpG进行T细胞依赖刺激;通过流细胞计,ELISpot和ELISA进行分析.
主要成果:
- 在适当的刺激下,CVID患者的MBCs在体外分化为IgG和IgMASC,特别是在II议定书下.
- 虽然ex vivo类切换的MBCs减少了,但体外分化和扩散与对照相比较.
- 刺激后IgA分泌仍然明显受损;检测到特定的IgG反应,没有自身抗体的出现.
结论:
- 在T细胞依赖刺激下,CVID患者的MBC保留了功能B细胞分化和抗原特异性IgG分泌能力.
- 在CVID中,IgA分泌仍然是一个显著的缺陷.
- 该研究方法为研究恢复MBC功能和CVID中的抗原特异性反应的策略提供了一个平台.
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