Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
PLoS One. 2011;6(8):e22365. doi: 10.1371/journal.pone.0022365. Epub 2011 Aug 4.
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.
抗体的保护、病理和治疗特性源于其巨大的多样性。这种多样性在潜力上几乎是无限的，但实际的多样性仍未被充分理解。在这里，我们使用深度测序来描述重链 CDR3 区域的多样性，CDR3 区域是抗体结合特异性的最重要贡献者，以及组成它的 V、D 和 J 片段。我们发现，在逐步的 D-J 和 V-DJ 重组事件中，D 段和 J 段的选择相互之间存在一些偏向；然而，我们发现 V 段的选择基本上与两者都无关。V、D 和 J 片段的利用频率不同，导致 VDJ 组合在库中的表示高度偏斜。然而，两个人的 CDR3 库之间观察到的片段使用模式几乎完全相同。V、D 和 J 片段的使用和重组模式不足以解释两个人的 CDR3 库之间的重叠。最后，我们发现虽然理论上存在近无限数量的重链 CDR3，但成年人血液中的 CDR3 约有 300 万至 900 万种。
