AID Activity in B Cells Strongly Correlates with Polyclonal Antibody Affinity Maturation in-vivo Following Pandemic 2009-H1N1 Vaccination in Humans
AID Activity in B Cells Strongly Correlates with Polyclonal Antibody Affinity Maturation in-vivo Following Pandemic 2009-H1N1 Vaccination in Humans
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DOI：
10.1371/journal.ppat.1002920
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发表时间：
2012-09-01
期刊：
影响因子：
6.7
通讯作者：
Golding, Hana
中科院分区：
文献类型：
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作者：
Khurana, Surender;Frasca, Daniela;Golding, Hana
激活诱导胞苷脱氨酶 (AID) 在体细胞超突变和多克隆抗体亲和力成熟中的作用尚未在人类多克隆反应中得到证实。我们研究了 H1N1pdm09 疫苗接种后人类 B 细胞中 AID 的诱导是否与针对年轻人和老年人血浆中血凝素结构域的体内抗体亲和力成熟相关。通过 qPCR 对来自不同年龄的接种 H1N1pdm09 流感疫苗的个体的 B 细胞进行 AID 测量。使用表面等离子共振中的实时动力学，通过抗体-抗原复合物解离速率来测量人血浆中的多克隆抗体对 H1N1pdm09 血凝素的 HA1 和 HA2 结构域的亲和力。结果显示，接种 H1N1pdm09 疫苗后，B 细胞中 AID 诱导能力与年龄相关。疫苗接种前的 AID mRNA 水平和 H1N1pdm09 疫苗接种后 AID mRNA 表达的倍数增加与多克隆抗体对 HA1 球状结构域（但与保守的 HA2 茎）亲和力的增加直接相关。在较年轻的人群中，观察到与 HA1 球状结构域的显着亲和力成熟，这与 AID 的初始水平和疫苗接种后 AID 的倍数增加相关。在一些老年个体（> 65 岁）中，在接种疫苗之前观察到对 HA1 结构域的较高亲和力，并且 H1N1pdm09 疫苗接种导致抗体亲和力变化最小，这与该年龄组中 AID 诱导率较低相关。这些发现首次证明了人类 AID 诱导与体内抗体亲和力成熟之间的密切相关性。产生高亲和力抗体的能力可能对阐明疫苗接种后的年龄特异性抗体反应以及最终的临床疗效和疾病结果产生重大影响。
The role of Activation-Induced Cytidine Deaminase (AID) in somatic hypermutation and polyclonal antibody affinity maturation has not been shown for polyclonal responses in humans. We investigated whether AID induction in human B cells following H1N1pdm09 vaccination correlated with in-vivo antibody affinity maturation against hemagglutinin domains in plasma of young and elderly individuals. AID was measured by qPCR in B cells from individuals of different ages immunized with the H1N1pdm09 influenza vaccine. Polyclonal antibody affinity in human plasma for the HA1 and HA2 domains of the H1N1pdm09 hemagglutinin was measured by antibody-antigen complex dissociation rates using real time kinetics in Surface Plasmon Resonance. Results show an age-related decrease in AID induction in B cells following H1N1pdm09 vaccination. Levels of AID mRNA before vaccination and fold-increase of AID mRNA expression after H1N1pdm09 vaccination directly correlated with increase in polyclonal antibody affinity to the HA1 globular domain (but not to the conserved HA2 stalk). In the younger population, significant affinity maturation to the HA1 globular domain was observed, which associated with initial levels of AID and fold-increase in AID after vaccination. In some older individuals (>65 yr), higher affinity to the HA1 domain was observed before vaccination and H1N1pdm09 vaccination resulted in minimal change in antibody affinity, which correlated with low AID induction in this age group. These findings demonstrate for the first time a strong correlation between AID induction and in-vivo antibody affinity maturation in humans. The ability to generate high affinity antibodies could have significant impact on the elucidation of age-specific antibody responses following vaccination and eventual clinical efficacy and disease outcome.