Invasion of spontaneous germinal centers by naive B cells is rapid and persistent.
Invasion of spontaneous germinal centers by naive B cells is rapid and persistent.
复制标题
初始 B 细胞对自发生发中心的侵袭是快速且持久的。
DOI：
10.1101/2023.05.30.542805
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Carroll,MC
中科院分区：
文献类型：
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作者：
vandenBroek,T;Oleinika,K;Rahmayanti,S;Castrillon,C;vanderPoel,CE;Carroll,MC
在由单个流氓B细胞克隆启动的自身反应性生发中心（GC）中，野生型B细胞扩增并产生靶向其他自身抗原的克隆，称为表位扩散。表位扩散的慢性、进行性需要早期干预，但野生型B细胞入侵和参与GC的动力学和分子要求在很大程度上仍然未知。在系统性红斑狼疮小鼠模型中，通过异种共生和过继性转移方法，我们证明了野生型B细胞快速加入现有的GCs，克隆扩增，持续存在，并有助于自身抗体的产生和多样化。自身反应性GCs的侵袭需要TLR7、B细胞受体特异性、抗原呈递和I型干扰素信号。过继传递模型为识别自身免疫中B细胞耐受性破坏的早期事件提供了一种新的工具。
In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a novel tool for identifying early events in the breaking of B cell tolerance in autoimmunity.