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识别人类骨髓中自动反应蛋白酶3+B细胞的中央耐受性检查点

Alvise Berti¹, Michele Tomasi², Isabella Pesce³

¹Rheumatology Unit, Santa Chiara Regional Hospital, APSS, Trento, Italy; Center for Medical Sciences (CISMed), Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy; Laboratory of Synthetic and Structural Vaccinology, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy.

Journal of autoimmunity

|November 16, 2024

概括

针对蛋白酶3 (PR3) 的自身反应性B细胞在骨髓中经历了严格的选择. 这个中央耐受性检查点在进入外围之前有效地去除大多数PR3阳性B细胞,防止自身免疫.

科学领域:

免疫学免疫学免疫学
这是一种自身免疫力.
细胞生物学细胞生物学

背景情况:

与ANCA相关的血管炎 (AAV) 涉及针对髓氧化酶 (MPO) 和蛋白酶3 (PR3) 的抗体.
产生高亲和力MPO-和PR3-ANCA的自反应性B细胞由中央和外围的耐受性检查点来调节.
对于自身反应性PR3阳性B细胞的周围耐受性机制已被理解,但骨髓中的中心耐受性仍然不太清楚.

研究的目的:

研究控制骨髓 (BM) 中不成熟的PR3-阳性 (PR3+) B细胞的中央耐受机制.
为了比较BM和外围血液中PR3+B细胞的表型和频率.
阐明骨髓耐受性检查点在预防PR3相关自身免疫的作用.

主要方法:

流细胞计用于识别和量化PR3+B细胞,使用标记的复合PR3 (rPR3).
从非血管炎对照 (无AAV) 中分析了BM单核细胞 (BMMC) 和外周血液单核细胞 (PBMC) 的对样本.
来自患有PR3-ANCA相关血管炎 (PR3-AAV) 的患者的PBMC也被分析用于比较.

主要成果:

在没有AAV的对照组中,BMMC中发现PR3+B细胞的比例高于PBMC (1.98%与0.9%,p <0.01).
在CD24++CD38++B细胞子集 (面向外围) 中,BMMC的PR3+B细胞比PBMC在No-AAV中的比例更高 (3.35%对1.23%,p <0.01).
在BMMC内观察到PR3+部分从不成熟 (IgD-IgM+) 到早期过渡 (IgD+IgM+) B细胞的显著下降 (2.80%对1.76%,p <0.01),表明选择.

结论:

自主反应的PR3+B细胞在骨髓中受到严格的选择.
在BM中,中央耐受性检查点对于去除PR3+B细胞至关重要,主要是在不成熟和早期过渡阶段之间.
这种骨髓选择过程对于预防与PR3相关的自身免疫性至关重要.

关键词:

与ANCA相关的血管炎自主反应性B细胞骨髓骨髓骨髓骨髓骨髓中央宽容检查点的检查点.带有多阳性炎的粒状瘤.蛋白酶 3 蛋白质酶 3 的作用.

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