title: Antibody V(h) repertoire differences between resolving and chronically evolving hepatitis C virus infections.
abstract: Despite the production of neutralizing antibodies to hepatitis C virus (HCV), many patients fail to clear the virus and instead develop chronic infection and long-term complications. To understand how HCV infection perturbs the antibody repertoire and to identify molecular features of antibody genes associated with either viral clearance or chronic infection, we sequenced the V(D)J region of naïve and memory B cells of 6 persons who spontaneously resolved an HCV infection (SR), 9 patients with a newly diagnosed chronically evolving infection (CE), and 7 healthy donors. In both naïve and memory B cells, the frequency of use of particular antibody gene subfamilies and segments varied among the three clinical groups, especially between SR and CE. Compared to CE, SR antibody genes used fewer VH, D and JH gene segments in naïve B cells and fewer VH segments in memory B cells. SR and CE groups significantly differed in the frequency of use of 7 gene segments in naïve B cell clones and 3 gene segments in memory clones. The nucleotide mutation rates were similar among groups, but the pattern of replacement and silent mutations in memory B cell clones indicated greater antigen selection in SR than CE. Greater clonal evolution of SR than CE memory B cells was revealed by analysis of phylogenetic trees and CDR3 lengths. Pauciclonality of the peripheral memory B cell population is a distinguishing feature of persons who spontaneously resolved an HCV infection. This finding, previously considered characteristic only of patients with HCV-associated lymphoproliferative disorders, suggests that the B cell clones potentially involved in clearance of the virus may also be those susceptible to abnormal expansion.
authors: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. v.racanelli@dimo.uniba.it
authors: Vito
authors: V
authors: Racanelli
authors: Claudia
authors: C
authors: Brunetti
authors: Valli
authors: V
authors: De Re
authors: Laura
authors: L
authors: Caggiari
authors: Mariangela
authors: M
authors: De Zorzi
authors: Patrizia
authors: P
authors: Leone
authors: Federico
authors: F
authors: Perosa
authors: Angelo
authors: A
authors: Vacca
authors: Franco
authors: F
authors: Dammacco
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012075:Remission, Spontaneous; D017422:Sequence Analysis, DNA
chemical_list: D000914:Antibodies, Viral; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region