The NTCP interacts directly with the preS1 domain of the HBV surface antigen (HBsAg), and antibodies against HBsAg could block the virus entry into cells, neutralize the virus, and restrict the spread of HBV ( Wu et al., 2019 Yan et al., 2019). Notably, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as the receptor of HBV has largely advanced our understanding of humoral immune responses and anti-HBV antibodies during chronic HBV infection, which was largely neglected in previous HBV studies ( Yan et al., 2012 Ni et al., 2014). Recently, several such agents have been developed to reconstitute host responses including lymphotoxin-β receptor agonists, toll-like receptor agonists, immune checkpoint inhibitors, and therapeutic vaccines ( Gehring and Protzer, 2019).
#Antibody repertoire dominated by few clones series
Thus, a series of strategies were designed to restore human immunity and resolve the infection. Generally, defective immune responses, particularly the exhaustion of T lymphocytes, were commonly observed during chronic HBV infection. 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). The virus-host interaction during HBV infection determines infection outcome. However, current therapies using interferon or direct-acting antiviral agents are unlikely to eradicate the virus or cure the infection ( Gish et al., 2012 Revill et al., 2016) thus, efficient therapeutic approaches are urgent requirements.
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). Taken together, our findings provide a better understanding of the antibody repertoires of HBV chronically infected individuals.Ĭhronic hepatitis B is a major global health issue. 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. In contrast, for IgG repertories, the preferred used VDJ genes were similar in all the three populations. 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. More shared antibody clones were found between the IgM repertoires of IHB and HH than that found between CHB and HH (7079 clones vs. Such difference in clone diversity and expansion was not observed in the IgG repertoires of the three populations. 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). 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.
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. High-throughput antibody sequencing allows in-depth insights into human antibody repertoires. 3Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai, China.2Traditional Chinese Medicine Department, Rehabilitation Hospital, Quanzhou, China.
1Central Laboratory, Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.Binbin Hong 1*, Lizhi Wang 2, Chunlan Huang 2, Xiaoju Hong 2, Alan Liu 2, Qiulan Li 1, Qiaoling Liu 1, Lili Su 1, Lixing Wang 1, Chunyu Wang 3 and Tianlei Ying 3*
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