V(D)J recombination, somatic hypermutation and class switch recombination of immunoglobulins: mechanism and regulation

• Published in: Immunology Vol. 160; no. 3; pp. 233 - 247
• Main Authors: Chi, Xiying, Li, Yue, Qiu, Xiaoyan
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2020; John Wiley and Sons Inc
• Subjects: Antibodies; Antigens; B cell; Chromosomes; class switch recombination; Class switching; Deoxyribonucleic acid; DNA; Exons; Genetics; Immune system; Immunoglobulins; J gene; Lymphocytes; Lymphocytes B; mechanism; Regulatory mechanisms (biology); Review; Segments; Somatic hypermutation; V(D)J recombination; Vertebrates; B cell; somatic hypermutation; mechanism; class switch recombination; V(D)J recombination
• ISSN: 0019-2805; 1365-2567; 1365-2567
• DOI: 10.1111/imm.13176

Summary Immunoglobulins emerging from B lymphocytes and capable of recognizing almost all kinds of antigens owing to the extreme diversity of their antigen‐binding portions, known as variable (V) regions, play an important role in immune responses. The exons encoding the V regions are known as V (variable), D (diversity), or J (joining) genes. V, D, J segments exist as multiple copy arrays on the chromosome. The recombination of the V(D)J gene is the key mechanism to produce antibody diversity. The recombinational process, including randomly choosing a pair of V, D, J segments, introducing double‐strand breaks adjacent to each segment, deleting (or inverting in some cases) the intervening DNA and ligating the segments together, is defined as V(D)J recombination, which contributes to surprising immunoglobulin diversity in vertebrate immune systems. To enhance both the ability of immunoglobulins to recognize and bind to foreign antigens and the effector capacities of the expressed antibodies, naive B cells will undergo class switching recombination (CSR) and somatic hypermutation (SHM). However, the genetics mechanisms of V(D)J recombination, CSR and SHM are not clear. In this review, we summarize the major progress in mechanism studies of immunoglobulin V(D)J gene recombination and CSR as well as SHM, and their regulatory mechanisms. Developments of novel experimental methodologies and analysis techniques have elucidated more molecules and mechanisms concerning the generation and regulation of immunoglobulin. This review summarizes the current state of research concerning the mechanism of immunoglobulin V(D)J recombination, CSR as well as SHM, and their regulatory mechanisms.