Shi Zhan, Zhang Qingyang, Yan Huige, Yang Ying, Wang Pingzhang, Zhang Yixiao, Deng Zhenling, Yu Meng, Zhou Wenjing, Wang Qianqian, Yang Xi, Mo Xiaoning, Zhang Chi, Huang Jing, Dai Hui, Sun Baofa, Zhao Yongliang, Zhang Liang, Yang Yun-Gui, Qiu Xiaoyan
1Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191 China.
2NHC Key Laboratory of Medical Immunology, Peking University, Beijing, 100191 China.
Cell Discov. 2019 Dec 10;5:64. doi: 10.1038/s41421-019-0137-3. eCollection 2019.
Antibodies have a common structure consisting of two identical heavy (H) and two identical light (L) chains. It is widely accepted that a single mature B cell produces a single antibody through restricted synthesis of only one VDJ (encoding the H-chain variable region) and one VJ (encoding the L-chain variable region) via recombination. Naive B cells undergo class-switch recombination (CSR) from initially producing membrane-bound IgM and IgD to expressing more effective membrane-bound IgG, IgA, or IgE when encountering antigens. To ensure the "one cell - one antibody" paradigm, only the constant region of the H chain is replaced during CSR, while the rearranged VDJ pattern and the L chain are kept unchanged. To define those long-standing classical concepts at the single-cell transcriptome level, we applied the Chromium Single-Cell Immune Profiling Solution and Sanger sequencing to evaluate the Ig transcriptome repertoires of single B cells. Consistent with the "one cell - one antibody" rule, most of the B cells showed one V(D)J recombination pattern. Intriguingly, however, two or more VDJ or VJ recombination patterns of IgH chain or IgL chain were also observed in hundreds to thousands of single B cells. Moreover, each Ig class showed unique VDJ recombination pattern in a single B-cell expressing multiple Ig classes. Together, our findings reveal an unprecedented presence of multi-Ig specificity in some single B cells, implying regulation of Ig gene rearrangement and class switching that differs from the classical mechanisms of both the "one cell - one antibody" rule and CSR.
抗体具有共同的结构，由两条相同的重链（H）和两条相同的轻链（L）组成。人们普遍认为，单个成熟B细胞通过重组仅限制合成一个VDJ（编码重链可变区）和一个VJ（编码轻链可变区）来产生单一抗体。初始B细胞在遇到抗原时会经历类别转换重组（CSR），从最初产生膜结合型IgM和IgD转变为表达更有效的膜结合型IgG、IgA或IgE。为确保“一个细胞 - 一种抗体”模式，在CSR过程中仅重链的恒定区被替换，而重排的VDJ模式和轻链保持不变。为了在单细胞转录组水平上定义这些长期存在的经典概念，我们应用了铬单细胞免疫分析解决方案和桑格测序来评估单个B细胞的Ig转录组库。与“一个细胞 - 一种抗体”规则一致，大多数B细胞显示出一种V（D）J重组模式。然而，有趣的是，在数百到数千个单个B细胞中也观察到了两条或更多条IgH链或IgL链的VDJ或VJ重组模式。此外，在表达多种Ig类别的单个B细胞中，每种Ig类别都显示出独特的VDJ重组模式。总之，我们的研究结果揭示了一些单个B细胞中前所未有的多Ig特异性的存在，这意味着Ig基因重排和类别转换的调控不同于“一个细胞 - 一种抗体”规则和CSR的经典机制。
