Hepatitis C virus, B-cell proliferation and lymphomas.
Accumulating evidence support a role for hepatitis C virus (HCV) in the pathogenesis of human lymphoproliferative disorders. Clonal expansions of B lymphocytes have been prevalently detected in the bone marrow, in the liver and in the peripheral blood of HCV-infected patients. Epidemiologic studies have associated HCV infection with an increased risk of B-cell lymphoma development, particularly of those with primary localization to organs target of HCV infection. The analysis of the B-cell receptor variable region sequences in sequential phases of HCV-associated lymphomas provided evidence of an ongoing somatic mutation process still present in the neoplastic cells. A restricted repertoire of V, D, J genes was used to assemble the B-cell receptor, and a frequent occurrence of certain gene combinations (V1-69/D3-22/J4 heavy chain with a V3-20 encoded light chain; V3-7/D3/J3 heavy chain with V3-15/J1 light chain; V3-231D3-22/J4 or V4-59/D2-15/J2 with a V3-20 light chain) was observed, thus suggesting a common antigen-binding specificity for these B-cell clones. The high similarity to antibodies with rheumatoid factor (RF) activity as well as to anti-HCV E2 antibodies suggested that HCV, alone or in complex with IgG, could play a pathogenetic role as an exogenous trigger in certain stages of B-cell lymphoproliferation and in certain subsets of B-cell non-Hodgkin's lymphomas (NHLs). The restricted gene repertoire used to assemble the B-cell receptor observed in HCV-associated B-cell NHLs could have important implications as an antigenic target in anti-tumor immunologic therapies.
Gasparotto
Daniela
D
Division of Experimental Oncology, Centro di Riferimento Oncologico, Aviano (PN), Italy.
De Re
Valli
V
Boiocchi
Mauro
M
D001402:B-Lymphocytes / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division; D015321:Gene Rearrangement; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000628:therapy; D011947:Receptors, Antigen, B-Cell / Q000502:physiology
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell