Luo Zhonghui, Ronai Diana, Scharff Matthew D
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J Allergy Clin Immunol. 2004 Oct;114(4):726-35; quiz 736. doi: 10.1016/j.jaci.2004.07.049.
Before exposure to antigen, antibodies with a wide diversity of antigen-binding sites are created by V(D)J rearrangement. After exposure to antigen, further diversification is accomplished by means of somatic hypermutation of the antibody variable region genes and class-switch recombination between the heavy-chain mu constant region and the downstream gamma, epsilon, and alpha constant region. The variable region mutations are responsible for the affinity maturation of the antibody response, whereas class-switch recombination enables the antibodies to be distributed throughout the body and to carry out different effector functions. Both somatic mutation and class switching require an enzyme called activation-induced cytidine deaminase (AID) that converts deoxycytidines to deoxyuracils on single-stranded DNA. Genetic defects of AID in human subjects result in hyper-IgM syndrome type 2. The analysis of both mutant mice and immunodeficient patients has led to a better understanding of the mechanism of action and role of AID in immunity, as well as in the malignant transformation of B cells.
在接触抗原之前，通过V(D)J重排产生具有广泛多样抗原结合位点的抗体。接触抗原后，通过抗体可变区基因的体细胞超突变以及重链μ恒定区与下游γ、ε和α恒定区之间的类别转换重排实现进一步的多样化。可变区突变负责抗体应答的亲和力成熟，而类别转换重排使抗体能够分布于全身并执行不同的效应功能。体细胞突变和类别转换都需要一种称为活化诱导胞苷脱氨酶（AID）的酶，该酶可将单链DNA上的脱氧胞苷转化为脱氧尿嘧啶。人类受试者中AID的遗传缺陷会导致2型高IgM综合征。对突变小鼠和免疫缺陷患者的分析有助于更好地理解AID在免疫以及B细胞恶性转化中的作用机制和角色。
