Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas
Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas
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DOI：
10.1038/nature714
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发表时间：
2002-02-14
期刊：
影响因子：
64.8
通讯作者：
Scharff, MD
中科院分区：
文献类型：
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作者：
Martin, A;Bardwell, PD;Scharff, MD
高亲和力保护性抗体的产生需要抗体可变（V）区基因的体细胞超突变（SHM）。 SHM 的特点是点突变频率高，仅发生在 B 细胞分化的中心母细胞阶段。此过程需要激活诱导的胞苷脱氨酶 (AID)，该酶在生发中心中心母细胞中特异性表达 (1)，但其确切作用尚不清楚 (2)。在这里，我们表明，在类中心母细胞Ramos细胞中，AID是SHM所必需的，并且AID的表达足以在杂交瘤细胞中诱导SHM，杂交瘤细胞代表通常不经历SHM的B细胞分化的后期阶段。在一种杂交瘤中，突变仅发生在 G.C 碱基对中，大部分位于 RGYW 或 WRCY 基序内，表明 AID 对这些核苷酸的突变负有主要责任。杂交瘤中 SHM 的激活表明 AID 不需要其他中心母细胞特异性辅因子来诱导 SHM，这表明它要么单独发挥作用，要么它所需的因子在 B 细胞分化的其他阶段表达。
The production of high-affinity protective antibodies requires somatic hypermutation (SHM) of the antibody variable (V) region genes. SHM is characterized by a high frequency of point mutations that occur only during the centroblast stage of B-cell differentiation. Activation-induced cytidine deaminase (AID), which is expressed specifically in germinal-centre centroblasts(1), is required for this process, but its exact role is unknown(2). Here we show that AID is required for SHM in the centroblast-like Ramos cells, and that expression of AID is sufficient to induce SHM in hybridoma cells, which represent a later stage of B-cell differentiation that does not normally undergo SHM. In one hybridoma, mutations were exclusively in G.C base pairs that were mostly within RGYW or WRCY motifs, suggesting that AID has primary responsibility for mutations at these nucleotides. The activation of SHM in hybridomas indicates that AID does not require other centroblast-specific cofactors to induce SHM, suggesting either that it functions alone or that the factors it requires are expressed at other stages of B-cell differentiation.