哺乳动物抗体多样性产生机制及其在合成生物学中的应用

Generation of antibody diversity in mammals: mechanisms and synthetic biology applications

摘要:

免疫球蛋白(immunoglobulin, Ig)是有颌类脊椎动物特有的一类适应性免疫效应分子，其高度多样性的产生依赖于V(D)J基因重排、体细胞超突变(somatic hypermutation, SHM)和抗体类别转换重组(class switch recombination, CSR)等机制。上述过程由多种关键酶协同调控，包括重组激活酶(recombination activating gene, RAG)、末端脱氧核苷酸转移酶(terminal deoxynucleotidyl transferase, TdT)、活化诱导型胞苷脱氨酶(activation-induced cytidine deaminase, AID)及DNA糖基化酶等。这些酶不仅在抗原受体多样性形成中发挥关键作用，也被广泛开发为进行生物学基础研究的重要工具。本文综述了哺乳动物抗原受体多样性形成的分子机制，探讨了抗体筛选与应用的研究进展，并重点梳理了TdT、胞苷脱氨酶及DNA糖基化酶在合成生物学领域中的最新应用。相关研究为生物技术与医学领域的基础研究和技术创新提供了重要理论支撑与新方向。

Abstract:

Immunoglobulins are adaptive immune effector molecules unique to jawed vertebrates. Their remarkable diversity relies on mechanisms including V(D)J recombination, somatic hypermutation, and class switch recombination. These processes are orchestrated by a variety of key enzymes, such as recombination-activating gene proteins, terminal deoxynucleotidyl transferase (TdT), activation-induced cytidine deaminase, and DNA glycosylases. These enzymes not only play critical roles in the formation of antigen receptor diversity but have also been widely developed as useful tools for basic biological research. This review summarizes the molecular mechanisms underlying antigen receptor diversification in mammals, discusses recent progress in antibody screening and application, and highlights the latest advances in the use of TdT, cytidine deaminases, and DNA glycosylases in synthetic biology. These studies provide important theoretical support and new directions for fundamental research and technological innovation in biotechnology and medicine.