Liu Jia-Chen, Zhang Ke, Zhang Xu, Guan Fei, Zeng Hu, Kubo Masato, Lee Pamela, Candotti Fabio, James Louisa Katherine, Camara Niels Olsen Saraiva, Benlagha Kamel, Lei Jia-Hui, Forsman Huamei, Yang Lu, Xiao Wei, Liu Zheng, Liu Chao-Hong
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China.
Department of Pathogen Biology School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology Wuhan Hubei China.
MedComm (2020). 2024 Aug 13;5(8):e662. doi: 10.1002/mco2.662. eCollection 2024 Aug.
Maturation of the secondary antibody repertoire requires class-switch recombination (CSR), which switches IgM to other immunoglobulins (Igs), and somatic hypermutation, which promotes the production of high-affinity antibodies. Following immune response or infection within the body, activation of T cell-dependent and T cell-independent antigens triggers the activation of activation-induced cytidine deaminase, initiating the CSR process. CSR has the capacity to modify the functional properties of antibodies, thereby contributing to the adaptive immune response in the organism. Ig CSR defects, characterized by an abnormal relative frequency of Ig isotypes, represent a rare form of primary immunodeficiency. Elucidating the molecular basis of Ig diversification is essential for a better understanding of diseases related to Ig CSR defects and could provide clues for clinical diagnosis and therapeutic approaches. Here, we review the most recent insights on the diversification of five Ig isotypes and choose several classic diseases, including hyper-IgM syndrome, Waldenström macroglobulinemia, hyper-IgD syndrome, selective IgA deficiency, hyper-IgE syndrome, multiple myeloma, and Burkitt lymphoma, to illustrate the mechanism of Ig CSR deficiency. The investigation into the underlying mechanism of Ig CSR holds significant potential for the advancement of increasingly precise diagnostic and therapeutic approaches.
次级抗体库的成熟需要类别转换重组（CSR），它将IgM转换为其他免疫球蛋白（Ig），以及体细胞高频突变，后者促进高亲和力抗体的产生。在体内发生免疫反应或感染后，T细胞依赖性和T细胞非依赖性抗原的激活会触发激活诱导的胞苷脱氨酶的激活，从而启动CSR过程。CSR有能力改变抗体的功能特性，从而有助于机体的适应性免疫反应。以Ig同种型的相对频率异常为特征的Ig CSR缺陷是原发性免疫缺陷的一种罕见形式。阐明Ig多样化的分子基础对于更好地理解与Ig CSR缺陷相关的疾病至关重要，并可为临床诊断和治疗方法提供线索。在此，我们综述了关于五种Ig同种型多样化的最新见解，并选择了几种经典疾病，包括高IgM综合征、华氏巨球蛋白血症、高IgD综合征、选择性IgA缺乏症、高IgE综合征、多发性骨髓瘤和伯基特淋巴瘤，以说明Ig CSR缺陷的机制。对Ig CSR潜在机制的研究对于推进日益精确的诊断和治疗方法具有巨大潜力。
