Exceptional Antibodies Produced by Successive Immunizations.
Exceptional Antibodies Produced by Successive Immunizations.
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DOI：
10.1371/journal.pbio.1002321
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发表时间：
2015-12
期刊：
影响因子：
9.8
通讯作者：
Russell Knode LM
中科院分区：
文献类型：
--
作者：
Gearhart PJ;Castiblanco DP;Russell Knode LM
抗体站在我们和病原体之间。病毒迅速变异以避免被发现，抗体也以相似的速度变异以追捕它们。这种死亡螺旋是由改变DNA序列的特殊蛋白质和易出错的聚合酶推动的。在这里，我们探讨了B淋巴细胞如何通过表达激活诱导的脱氨酶来保持竞争，这在免疫球蛋白位点中释放了突变的海啸。这产生了随机的DNA替换，随后选择了亲和力最高的抗体。我们也许能够通过连续接种来扩大特定B细胞的数量，从而操纵这一过程，产生更好的抗体。本文探讨了通过使用工程抗原进行系列疫苗接种来操纵B淋巴细胞体细胞超突变的可能性，目的是产生有效的抗体来破坏病原体。
Antibodies stand between us and pathogens. Viruses mutate quickly to avoid detection, and antibodies mutate at similar rates to hunt them down. This death spiral is fueled by specialized proteins and error-prone polymerases that change DNA sequences. Here, we explore how B lymphocytes stay in the race by expressing activation-induced deaminase, which unleashes a tsunami of mutations in the immunoglobulin loci. This produces random DNA substitutions, followed by selection for the highest affinity antibodies. We may be able to manipulate the process to produce better antibodies by expanding the repertoire of specific B cells through successive vaccinations. This Essay explores the possibility of manipulating somatic hypermutation in B lymphocytes by administering serial vaccinations with engineered antigens, with the aim of generating potent antibodies to destroy pathogens.