Reconstructing a B-cell clonal lineage. I. Statistical inference of unobserved ancestors.
Reconstructing a B-cell clonal lineage. I. Statistical inference of unobserved ancestors.
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DOI：
10.12688/f1000research.2-103.v1
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kepler TB
中科院分区：
文献类型：
--
作者：
Kepler TB
对感染和免疫的适应性免疫应答中的关键现象之一是亲和力成熟，在此期间抗体基因被突变和选择，通常导致对引发抗原的结合亲和力的显著增加。多个方面的技术进步使得从单个B细胞克隆大量重链轻链对成为可能，从而鉴定整套克隆相关抗体。这些样本可以提供必要的信息来重建它们自己的历史--在克隆发展过程中引入谱系的变化序列--并详细研究亲和力成熟。但这样一个计划的成功完全取决于准确地推断创始祖先和其他未观察到的中间体。给定一组克隆相关的免疫球蛋白V区基因，这里描述的方法允许计算其可能的祖先的后验分布，从而彻底解释重建中固有的不确定性。我演示了这种方法在重链和轻链克隆中的应用，评估了推断的可靠性，并讨论了不确定性的来源。
One of the key phenomena in the adaptive immune response to infection and immunization is affinity maturation, during which antibody genes are mutated and selected, typically resulting in a substantial increase in binding affinity to the eliciting antigen. Advances in technology on several fronts have made it possible to clone large numbers of heavy-chain light-chain pairs from individual B cells and thereby identify whole sets of clonally related antibodies. These collections could provide the information necessary to reconstruct their own history - the sequence of changes introduced into the lineage during the development of the clone - and to study affinity maturation in detail. But the success of such a program depends entirely on accurately inferring the founding ancestor and the other unobserved intermediates. Given a set of clonally related immunoglobulin V-region genes, the method described here allows one to compute the posterior distribution over their possible ancestors, thereby giving a thorough accounting of the uncertainty inherent in the reconstruction. I demonstrate the application of this method on heavy-chain and light-chain clones, assess the reliability of the inference, and discuss the sources of uncertainty.