生发中心
过继性细胞移植
表位
B细胞
生物
自身免疫
免疫学
自身抗体
克隆(Java方法)
抛物线性
T细胞
细胞生物学
抗原
病毒学
抗体
免疫系统
遗传学
基因
作者
Theo van den Broek,Kristīne Oļeiņika,Siti Rahmayanti,Carlos Castrillón,Cees E. van der Poel,Michael Carroll
标识
DOI:10.1101/2023.05.30.542805
摘要
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.
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