Antibody V(h) repertoire differences between resolving and chronically evolving hepatitis C virus infections

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• Hepatitis C virus (HCV) infection often leads to chronic disease despite neutralizing antibody production.
• Understanding antibody repertoire perturbations is crucial for identifying factors influencing viral clearance versus chronic infection.

Purpose of the Study:

• To investigate how HCV infection impacts the antibody repertoire.
• To identify molecular features of antibody genes associated with spontaneous viral clearance or chronic HCV infection.

Main Methods:

• Sequencing of V(D)J regions in naïve and memory B cells from individuals with spontaneous HCV resolution (SR), chronic HCV infection (CE), and healthy donors.
• Analysis of antibody gene segment usage, nucleotide mutation rates, clonal evolution, and B cell population clonality.

Main Results:

• Significant differences in antibody gene subfamily and segment usage were observed between SR and CE groups in both naïve and memory B cells.
• Greater antigen selection and clonal evolution were evident in memory B cells of SR individuals compared to CE patients.
• Pauciclonality of the peripheral memory B cell population distinguished individuals who spontaneously resolved HCV infection.

Conclusions:

• Antibody gene usage and B cell repertoire dynamics differ significantly between spontaneous HCV clearance and chronic infection.
• The findings suggest that B cell clones involved in HCV clearance may also be prone to abnormal expansion.
• Pauciclonality in memory B cells is a key feature associated with spontaneous resolution of HCV infection.