常见的可变免疫缺陷IgM谱系狭窄地识别了红细胞和血小板糖
Carole Le Coz1, Melissa Trofa2, Dorothy L Butler3
1Division of Immunology and Allergy, Children's Hospital of Philadelphia, Philadelphia, Pa; Infinity, Toulouse Institute for Infectious and Inflammatory Diseases, University of Toulouse, CNRS, Inserm, Toulouse, France.
The Journal of allergy and clinical immunology
|May 1, 2024
概括
常见变性免疫缺陷 (CVID) 患者的自身免疫细胞衰竭与向抗原的IgM自身抗体有关. 这些自身抗体起源于生殖中心之外的边缘区域B细胞,有助于CVID的发病.
科学领域:
- 免疫学 免疫学 免疫学
- 这是一种自身免疫力.
- B细胞生物学B细胞生物学
背景情况:
- 自免疫细胞衰竭 (AIC) 在常见变性免疫缺陷 (CVID) 患者中很常见.
- 在CVID相关的AIC中,特定的自身抗体,它们的点和起源在很大程度上是未知的.
研究的目的:
- 在CVID患者中调查与AIC相关的IgM自身抗体的反应性,克隆性和来源.
- 了解B细胞子集和T毛囊辅助细胞在这些自身抗体的发展中的作用.
主要方法:
- 利用甘氨酸阵列,患者的红细胞和血小板来识别CVID IgM自身抗体的目标.
- 使用排序边缘区 (MZ) B细胞的IGH测序来分析自身反应性克隆.
- 通过显微镜和RNA测序,研究了MZ B细胞的功能和在桃体组织和淋巴结中的定位.
主要成果:
- 在有AIC (CVID+AIC) 的CVID患者中鉴定出自身反应性IgM,其向红细胞和血小板抗原.
- 在CVID+AIC患者的循环MZ B细胞中发现了多克隆I抗原识别B细胞受体的高度丰富.
- 观察到MZ B细胞在IL-10/IL-21激活后分泌IgM,特别是在与T毛囊辅助细胞共培养时,并注意到CVID+AIC淋巴结中Tfh和调节性T细胞的不平衡.
结论:
- 由MZ B细胞在生殖中心外产生的Glycan-reactive IgM自身抗体可能有助于CVID的自身免疫病理.
- 这些发现突出了CVID中自身抗体生产的潜在机制,并提出了治疗点.
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