Lower Somatic Mutation Levels in the λ Light-Chain Repertoires with Chronic HBV Infection

Binbin Hong,Qiulan Li,Lizhi Wang,Lili Su,Qiaoling Liu,Woon-Man Kung

doi:10.1155/2021/5525369

Abstract

To investigate the characteristics of the immunoglobulin light-chain repertoires with chronic HBV infection, the high-throughput sequencing and IMGT/HighV-QUEST were adapted to analyze the κ (IgK) and λ (IgL) light-chain repertoires from the inactive HBV carriers (IHB) and the healthy adults (HH). The comparative analysis revealed high similarity between the κ light-chain repertoires of the HBV carriers and the healthy adults. Nevertheless, the proportion of IGLV genes with ≥90% identity as the germline genes was higher in the IgL light-chain repertoire of the IHB library compared with that of HH library (74.6% vs. 69.1%). Besides, the frequency of amino acid mutations in the CDR1 regions was significantly lower in the IgL light-chain repertoire of the IHB library than that of the HH library (65.52% vs. 56.0%). These results suggested the lower somatic mutation level in the IgL repertoire of IHB library, which might indicate the biased selection of IGLV genes in the IgL repertoire with chronic HBV infection. These findings might lead to a better understanding of the characteristics of the light-chain repertoires of HBV chronically infected individuals.

Highlights

Hepatitis B virus infection is the major global health problem, despite the existence of hepatitis B vaccination [1, 2]
We found that the somatic hypermutation level in the IgL repertoire of the HBV carriers was lower than that of healthy adults
Total RNA was extracted and reverse-transcripted to the first-strand cDNA that was used as the template to amplify the antibody sequences. e PCR amplifications were performed using a set of sense primers highly aligned to the first seven codons of the V regions and antisense primers that exhibit specificity for the last eight codons at the 3′ ends of the constant domains corresponding to the numbering schemes of the IMGT database

Summary

Introduction

Hepatitis B virus infection is the major global health problem, despite the existence of hepatitis B vaccination [1, 2]. Most primary HBV infections are self-limiting with virus clearance and lifelong protective immunity; an estimated 3% to 5% of adults and up to 95% of children develop chronic HBV infection [3]. An extensive body of research suggested the neutralizing antibodies can prevent acute HBV infection and have a possibility to modulate the development of chronic HBV infection [4, 5]. Some characteristics of the antibody repertoire before and after HBV vaccination have been demonstrated using high-throughput sequencing [9,10,11]. Very few studies investigate the antibody repertoire of individuals with chronic HBV infection, and even less attention has been paid to the light-chain repertoire with HBV infection. Us, the characteristics of the light-chain repertoires with chronic HBV infection are less clear Very few studies investigate the antibody repertoire of individuals with chronic HBV infection, and even less attention has been paid to the light-chain repertoire with HBV infection. us, the characteristics of the light-chain repertoires with chronic HBV infection are less clear

Methods

Findings

Discussion

Conclusion