Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching
Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching
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DOI：
10.7554/elife.16578
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发表时间：
2016-08-02
期刊：
影响因子：
7.7
通讯作者：
Quake, Stephen R.
中科院分区：
文献类型：
--
作者：
Horns, Felix;Vollmers, Christopher;Quake, Stephen R.
抗体类别转换是适应性免疫系统的特征，其使得抗体的效应器特性多样化。尽管类别转换对于建立对病原体的保护性应答是必不可少的，但抗体类别转换的体内模式和谱系特征在活体人类中仍然没有表征。在这里，我们使用抗体库测序全面测量了人类成年双胞胎中抗体类别转换的景观。该图谱确定了每类抗体是如何产生的，并描绘了类转换途径的两层层次结构。使用体细胞超突变作为分子钟，我们发现密切相关的B细胞经常切换到同一类，但随着体细胞突变的积累而失去一致性。当纯化的B细胞在体外类别转换时，密切相关的细胞之间存在这种相关性，这表明类别转换重组是通过细胞自主印迹状态指向特定同种型的。
Antibody class switching is a feature of the adaptive immune system which enables diversification of the effector properties of antibodies. Even though class switching is essential for mounting a protective response to pathogens, the in vivo patterns and lineage characteristics of antibody class switching have remained uncharacterized in living humans. Here we comprehensively measured the landscape of antibody class switching in human adult twins using antibody repertoire sequencing. The map identifies how antibodies of every class are created and delineates a two-tiered hierarchy of class switch pathways. Using somatic hypermutations as a molecular clock, we discovered that closely related B cells often switch to the same class, but lose coherence as somatic mutations accumulate. Such correlations between closely related cells exist when purified B cells class switch in vitro, suggesting that class switch recombination is directed toward specific isotypes by a cell-autonomous imprinted state.