Hong Binbin, Wang Lizhi, Huang Chunlan, Hong Xiaoju, Liu Alan, Li Qiulan, Liu Qiaoling, Su Lili, Wang Lixing, Wang Chunyu, Ying Tianlei
Central Laboratory, Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.
Traditional Chinese Medicine Department, Rehabilitation Hospital, Quanzhou, China.
Front Microbiol. 2021 Jan 15;11:615669. doi: 10.3389/fmicb.2020.615669. eCollection 2020.
High-throughput antibody sequencing allows in-depth insights into human antibody repertoires. To investigate the characteristics of antibody repertoires in patients with chronic HBV infection, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of B lymphocytes from healthy adults and the HBV carriers with high or low level of viral replication. The comparative study revealed high levels of similarity between the IgM and IgG repertoires of the HBV carriers and the healthy adults, including the somatic mutations in V regions, the average CDR3 length, and the occurrence of junctional modifications. Nevertheless, the diversity of the unique clones decreased and some clusters of unique clones expanded in the IgM repertoire of chronic HBV carriers (CHB) compared with healthy adults (HH) and inactive HBV carriers (IHB). Such difference in clone diversity and expansion was not observed in the IgG repertoires of the three populations. More shared antibody clones were found between the IgM repertoires of IHB and HH than that found between CHB and HH (7079 clones vs. 2304 clones). Besides, the biased used IGHD genes were IGHD2-2 and IGHD3-3 in CHB library but were IGHD3-10 and IGHD3-22 in IHB and HH library. In contrast, for IgG repertories, the preferred used VDJ genes were similar in all the three populations. These results indicated that low level of serum HBV might not induce significant changes in BCR repertoires, and high level of HBV replication could have more impacts on IgM repertories than IgG repertoires. Taken together, our findings provide a better understanding of the antibody repertoires of HBV chronically infected individuals.
高通量抗体测序能够深入洞察人类抗体库。为了研究慢性乙型肝炎病毒（HBV）感染患者抗体库的特征，我们对健康成年人以及病毒复制水平高或低的HBV携带者的B淋巴细胞进行了Illumina测序和IMGT/HighV-QUEST分析。比较研究发现，HBV携带者与健康成年人的IgM和IgG抗体库之间存在高度相似性，包括V区的体细胞突变、平均互补决定区3（CDR3）长度以及连接修饰的发生情况。然而，与健康成年人（HH）和非活动性HBV携带者（IHB）相比，慢性HBV携带者（CHB）的IgM抗体库中独特克隆的多样性降低，一些独特克隆簇有所扩增。在这三个人群的IgG抗体库中未观察到克隆多样性和扩增的这种差异。与CHB和HH之间相比，在IHB和HH的IgM抗体库中发现了更多共享的抗体克隆（7079个克隆对2304个克隆）。此外，CHB文库中偏向使用的免疫球蛋白重链可变区基因（IGHD）是IGHD2-2和IGHD3-3，而在IHB和HH文库中是IGHD3-10和IGHD3-22。相比之下，对于IgG抗体库，在所有三个人群中偏好使用的V(D)J基因相似。这些结果表明，血清HBV水平低可能不会诱导B细胞受体（BCR）抗体库发生显著变化，并且HBV高复制水平对IgM抗体库的影响可能比对IgG抗体库的影响更大。综上所述，我们的研究结果有助于更好地了解慢性HBV感染个体的抗体库。
