Abstract
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.
Highlights
Chronic hepatitis B is a major global health issue
We found that most of the characteristics were similar in the immunoglobulin M (IgM) and immunoglobulin G (IgG) repertoires between healthy adults and hepatitis B virus (HBV) carriers
The diversity of unique clones decreased and some clones expanded in the IgM repertoire of chronic HBV carriers when compared with that of healthy adults and the inactive HBV carriers
Summary
Chronic hepatitis B is a major global health issue. More than 200 million people are persistently infected with the hepatitis B virus (HBV) worldwide, and are at high risk of developing liver cirrhosis and hepatocellular carcinoma (El-Serag, 2012; Trepo et al, 2014). Several reviews have summarized the current knowledge of host immune responses in chronic HBV infections (Bertoletti and Ferrari, 2012, 2016; Lin and Kao, 2016; Shin et al, 2016; Gehring and Protzer, 2019). A series of strategies were designed to restore human immunity and resolve the infection. Several such agents have been developed to reconstitute host responses including lymphotoxin-β receptor agonists, tolllike receptor agonists, immune checkpoint inhibitors, and therapeutic vaccines (Gehring and Protzer, 2019). Antibodies play important roles in limiting HBV infections and eliminating the virus
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