B-cell receptors expressed by lymphomas of hepatitis C virus (HCV)–infected patients rarely react with the viral proteins

• Published in: Blood 2014-03, Vol.123 (10), p.1512-1515
• Main Authors: Ng, Patrick P., Kuo, Chiung-Chi, Wang, Stanley, Einav, Shirit, Arcaini, Luca, Paulli, Marco, Portlock, Carol S., Marcotrigiano, Joseph, Tarr, Alexander, Ball, Jonathan, Levy, Ronald, Levy, Shoshana
• Format: Article
• Language: English
• Subjects: Animals; Brief Report; Cell Line; Genes, Immunoglobulin; Hepacivirus - genetics; Hepacivirus - immunology; Hepatitis C Antigens - immunology; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - immunology; Humans; Immunoglobulin G - genetics; Immunoglobulin G - immunology; Immunoglobulin M - genetics; Immunoglobulin M - immunology; Immunoglobulin Variable Region - genetics; Lymphoid Neoplasia; Lymphoma, B-Cell - complications; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - immunology; Lymphoma, B-Cell - metabolism; Receptors, Antigen, B-Cell - metabolism; Viral Proteins - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-10-532895

Chronic hepatitis C virus (HCV) infection has been implicated in the induction and maintenance of B-cell lymphomas. The strongest evidence for this derives from clinical observations of tumor regressions upon antiviral treatments. Here we used multiple methods to test the hypothesis that the expansion of HCV-specific B cells gives rise to lymphomas. We obtained lymphoma tissues from HCV-infected lymphoma patients, including some that later regressed upon antiviral treatments. We expressed the lymphoma B-cell receptors as soluble immunoglobulin Gs and membrane IgMs, and analyzed their reactivity with HCV proteins and with HCV virions. We confirmed previous reports that HCV-associated lymphomas use a restricted immunoglobulin variable region gene repertoire. However, we found no evidence for their binding to the HCV antigens. We conclude that most lymphomas of HCV-infected patients do not arise from B cells aimed at eliminating the virus. •We tested the hypothesis that B-cell lymphomas arising in HCV-infected patients express B-cell receptors specific to the virus.•We analyzed the reactivity of these B-cell receptors with HCV proteins using several experimental approaches, none of which supported the hypothesis.