First, it is known that patients' sera contain antibodies that have neutralizing properties in vitro. Īt present, knowledge about the B cell response to HCV in humans is limited to two kinds of data. However, studying the B cell (antibody) response to HCV has been extremely difficult due to the heterogeneous nature of HCV, the lack of a practical and readily available cell culture system to screen antibodies, and the limited resources for studying HCV infection in chimpanzees, the only species susceptible to HCV infection other than humans. Greater understanding of the B cell response to HCV may help predict the outcome of the infection in individual patients as well as their risk of developing lymphoproliferative disorders. It is therefore thought that B cells are largely ineffective in resolving HCV infection while they are responsible for its lymphoproliferative complications. The most prevalent of these complications are liver cirrhosis and hepatocellular carcinoma, but HCV-infected persons may also develop mixed cryoglobulinemia (MC) and B cell non-Hodgkin lymphoma (B-NHL) –. Although virus-specific antibodies are produced in essentially all persons infected with HCV, about 80% of these patients develop persistent infection and are at risk of long-term complications. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.ĭeciphering the humoral immune response to hepatitis C virus (HCV) has been challenging. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: The study was supported by a grant from the Associazione Italiana per la Ricerca sul Cancro, Milan, Italy. Received: Accepted: SeptemPublished: September 28, 2011Ĭopyright: © 2011 Racanelli et al. Gray, University of Cape Town, South Africa (2011) Antibody V h Repertoire Differences between Resolving and Chronically Evolving Hepatitis C Virus Infections. 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.Ĭitation: Racanelli V, Brunetti C, De Re V, Caggiari L, De Zorzi M, Leone P, et al. Pauciclonality of the peripheral memory B cell population is a distinguishing feature of persons who spontaneously resolved an HCV infection. Greater clonal evolution of SR than CE memory B cells was revealed by analysis of phylogenetic trees and CDR3 lengths. 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. 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. 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. 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. 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. 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.
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