近日，美国10×基因组学公司Wyatt J. McDonnell等研究人员合作发现，功能性抗体表现出轻链的一致性。相关论文发表在2022年10月26日在线发表在《自然》杂志上。

研究人员考虑了共享相同的重链V基因和CDRH3氨基酸序列并从不同供体分离出来的成对B细胞，也被称为公共克隆型。研究人员表明，对于初始型抗体（那些尚未适应抗原的抗体），它们使用相同的轻链V基因的概率约为10%，而对于记忆型（功能性）抗体，它约为80%，即使每个克隆型只使用一个细胞。功能性抗体的这种特性是一种现象，被称之为轻链一致性。当类似的重链在供体内反复出现时，研究人员也观察到这种现象。因此，尽管初始的抗体似乎是偶然复现的，但功能性抗体的复现揭示了V（D）J重组和免疫选择过程中令人惊讶的限制性和决定性。对于大多数功能性抗体，重链决定了轻链。

据了解，脊椎动物的适应性免疫系统修改了单个B细胞的基因组，从而编码结合特定抗原的抗体。在大多数哺乳动物中，抗体由重链和轻链组成，通过V、D（重链）、J和C基因片段的重组依次产生。每条链包含三个互补性决定区（CDR1-CDR3），它们有助于抗原特异性。某些重链和轻链对特定的抗原有优先权。

附：英文原文

Title: Functional antibodies exhibit light chain coherence

Author: Jaffe, David B., Shahi, Payam, Adams, Bruce A., Chrisman, Ashley M., Finnegan, Peter M., Raman, Nandhini, Royall, Ariel E., Tsai, FuNien, Vollbrecht, Thomas, Reyes, Daniel S., Hepler, N. Lance, McDonnell, Wyatt J.

Issue&Volume: 2022-10-26

Abstract: The vertebrate adaptive immune system modifies the genome of individual B cells to encode antibodies that bind particular antigens1. In most mammals, antibodies are composed of heavy and light chains that are generated sequentially by recombination of V, D (for heavy chains), J and C gene segments. Each chain contains three complementarity-determining regions (CDR1–CDR3), which contribute to antigen specificity. Certain heavy and light chains are preferred for particular antigens2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22. Here we consider pairs of B cells that share the same heavy chain V gene and CDRH3 amino acid sequence and were isolated from different donors, also known as public clonotypes23,24. We show that for naive antibodies (those not yet adapted to antigens), the probability that they use the same light chain V gene is around 10%, whereas for memory (functional) antibodies, it is around 80%, even if only one cell per clonotype is used. This property of functional antibodies is a phenomenon that we call light chain coherence. We also observe this phenomenon when similar heavy chains recur within a donor. Thus, although naive antibodies seem to recur by chance, the recurrence of functional antibodies reveals surprising constraint and determinism in the processes of V(D)J recombination and immune selection. For most functional antibodies, the heavy chain determines the light chain.

DOI: 10.1038/s41586-022-05371-z

Source: https://www.nature.com/articles/s41586-022-05371-z