Transcriptional control of activation-induced cytidine deaminase and error-prone DNA polymerases is functionally mature in the B cells of infants at birth
Transcriptional control of activation-induced cytidine deaminase and error-prone DNA polymerases is functionally mature in the B cells of infants at birth
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DOI：
10.1016/j.humimm.2006.02.021
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发表时间：
2006-01-01
期刊：
影响因子：
2.7
通讯作者：
Crowe, James E., Jr.
中科院分区：
文献类型：
--
作者：
Bowen, Amber L.;Tian, Cuixia;Crowe, James E., Jr.
免疫球蛋白基因的体细胞超突变（SHM）需要激活诱导胞苷脱氨酶（AID）。容易出错的DNA聚合酶，如Pol eta、Pol zeta和Pol iota，也参与了这一过程。与婴儿抗体相比，针对微生物病原体的成人抗体在亲和力和功能上有所增加。成人抗体通过体细胞突变实现这种增强的亲和力，这在婴儿的B细胞中是缺乏的。目前尚不清楚婴儿B细胞是否能够上调通过抗原受体刺激后引入突变所需的细胞机制。我们在这里表明，婴儿B细胞在通过B细胞受体刺激后，AID和pol - eta基因的转录表现出相似的动力学和量级，pol - iota和pol - zeta基因的转录水平仅略低。这些数据表明，上调介导SHM的酶的基因转录的能力并不是婴儿抗体反应功能质量的限制性决定因素。
Somatic hypermutation (SHM) of immunoglobulin genes requires activation-induced cytidine deaminase (AID). The error-prone DNA polymerases, such as Pol eta, Pol zeta, and Pol iota, also have been implicated in the process. Human adult antibodies directed to microbial pathogens are increased in affinity and function compared with those of infants. Adult antibodies achieve this increased affinity through somatic mutations, which are lacking in the B cells of infants. It is unknown if infant B cells are capable of upregulating the cell machinery needed to introduce mutations after stimulation through the antigen receptor. We show here that infant B cells exhibit similar kinetics and magnitude of transcription of AID and pol eta genes and only marginally lower levels of pol iota and pol zeta genes after stimulation through the B cell receptor. These data suggest that the ability to upregulate gene transcription of enzymes mediating SHM is not a limiting determinant of the functional quality of infant antibody responses.