Activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen and is associated with expansion of the primary antibody repertoire in the absence of exogenous antigens
Activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen and is associated with expansion of the primary antibody repertoire in the absence of exogenous antigens
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DOI：
10.1038/mi.2012.132
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发表时间：
2013-09-01
影响因子：
8
通讯作者：
Niku, M.
中科院分区：
文献类型：
--
作者：
Liljavirta, J.;Ekman, A.;Niku, M.
由于免疫球蛋白（Ig）基因的范围有限，牛和其他几种家畜依赖于组合后的初级库扩增。我们报道了激活诱导胞苷脱氨酶（AID）在胎牛回肠Peyer’s patch和脾脏中强烈表达，但在胎牛骨髓中不表达。IGHV（免疫球蛋白重链变量）突变的数量与AID表达相关。胎儿的突变特征与出生后和免疫后的犊牛相似，其靶向的是互补决定区（CDR）而不是框架区（FR）， CDR中的替代突变优先于沉默突变，而FRs中则不是，并且靶向AID热点基序RGYW/WRCY。统计分析表明，对话单存在负选择，对话单存在正选择。我们的研究结果表明，艾滋病介导的体细胞超突变和选择发生在牛胎儿中，这意味着在缺乏外源抗原的情况下，艾滋病在一抗库的多样化中发挥了作用。
Due to a limited range of immunoglobulin (Ig) genes, cattle and several other domestic animals rely on postrecombinatorial amplification of the primary repertoire. We report that activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen but not in fetal bone marrow. The numbers of IGHV (immunoglobulin heavy chain variable) mutations correlate with AID expression. The mutational profile in the fetuses is similar to postnatal and immunized calves, with targeting of complementarity-determining region (CDR) over framework region (FR), preference of replacement over silent mutations in CDRs but not in FRs, and targeting of the AID hotspot motif RGYW/WRCY. Statistical analysis indicates negative selection on FRs and positive selection on CDRs. Our results suggest that AID-mediated somatic hypermutation and selection take place in bovine fetuses, implying a role for AID in the diversification of the primary antibody repertoire in the absence of exogenous antigens.