High-resolution description of antibody heavy-chain repertoires in humans.

High-resolution description of antibody heavy-chain repertoires in humans.
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DOI:
10.1371/journal.pone.0022365
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Koralov SB
Koralov SB
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Arnaout R;Lee W;Cahill P;Honan T;Sparrow T;Weiand M;Nusbaum C;Rajewsky K;Koralov SB

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抗体的保护性、病理性和治疗性特性源于其相当大的多样性。这种多样性的潜力几乎是无限的,但实际的多样性仍然知之甚少。在这里,我们使用深度测序来表征重链CDR 3区的多样性,重链CDR 3区是抗体结合特异性的最重要贡献者,以及组成重链CDR 3区的V、D和J区段。我们发现,在逐步的D-J和V-DJ重组事件期间,D和J区段的选择对彼此施加一些偏差;然而,我们发现V段的选择基本上与两者无关。V、D和J段以不同的频率使用,导致在库中VDJ组合的高度偏斜的表示。然而,两个不同的个体之间的片段使用模式几乎是相同的。V、D和J区段使用和重组的模式不足以解释在两个个体的CDR 3库之间观察到的重叠。最后,我们发现,虽然原则上存在接近无限数量的重链CDR 3,但在成年人的血液中约有3-9百万个。
Antibodies' protective, pathological, and therapeutic properties result from their considerable diversity. This diversity is almost limitless in potential, but actual diversity is still poorly understood. Here we use deep sequencing to characterize the diversity of the heavy-chain CDR3 region, the most important contributor to antibody binding specificity, and the constituent V, D, and J segments that comprise it. We find that, during the stepwise D-J and then V-DJ recombination events, the choice of D and J segments exert some bias on each other; however, we find the choice of the V segment is essentially independent of both. V, D, and J segments are utilized with different frequencies, resulting in a highly skewed representation of VDJ combinations in the repertoire. Nevertheless, the pattern of segment usage was almost identical between two different individuals. The pattern of V, D, and J segment usage and recombination was insufficient to explain overlap that was observed between the two individuals' CDR3 repertoires. Finally, we find that while there are a near-infinite number of heavy-chain CDR3s in principle, there are about 3–9 million in the blood of an adult human being.
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