glycoprotein-e2--hepatitis-c-virus and Lymphoma--B-Cell

Topics: Cardiomyopathies; Cryoglobulinemia; Genes, bcl-2; Hepacivirus; HLA Antigens; Humans; Lichen Planus; Lymphoma, B-Cell; Nephritis; Porphyria Cutanea Tarda; Sjogren's Syndrome; Viral Envelope Proteins

We compared the E2-HVR1 region in HCV-1b positive B-NHL cases from a multicenter study with sequences from studies related to lymphoproliferative disorders and B cell compartmentalisation. We found rare and unique mutations both in B-NHL isolates and in cases with lymphoproliferative disorders and lymphocyte infection. These rare mutations could have an important effect on HVR1 region and, as a consequence, on the binding of E2 on CD81, with a possible implication for both antigenic stimulation and HCV entry. In conclusion, the HCV predominants circulating in B-NHL cases seem to be associated with clonal selection of rare variants.

Topics: Antigens, CD; Genetic Variation; Hepacivirus; Hepatitis C; Hepatitis C Antigens; Humans; Italy; Lymphoma, B-Cell; Molecular Sequence Data; Selection, Genetic; Species Specificity; Tetraspanin 28; Viral Envelope Proteins

To determine the prevalence of hepatitis C virus (HCV) infection in B-cell lymphoma in Japan. HCV infection and type II (monoclonal IgM) cryoglobulinaemia (CG) may be involved in the pathogenesis of low-grade B-cell lymphoma (ML) in southern Europe.. Forty-five (11.3%) of 400 B-cell ML cases were HCV antibody (Ab) positive, which was significantly (P < 0.01) higher than the blood donors (2.5%). Among them, 28 diffuse large B-cell lymphoma (DLBCL) cases were included. In the primary sites, 10 (47.6%) of 21 splenic DLBCL and seven (23.3%) of 30 gastric DLBCL were HCV Ab positive, which were significantly (P < 0.05) higher than the myeloma cases (4.9%). HCV infection was rarely (4.2%) detected in 24 lymphoplasmacytic and salivary gland low-grade B-cell ML cases. Type II CG was detected in one myeloma case (3.5%) of 29 HCV+ B-cell ML. By real-time polymerase chain reaction, HCV RNA was detected in fresh tumour tissues of all 11 B-cell ML cases examined. Lymphoma cells were positive for the envelope HCV non-structural (NS)3 and envelope (E2) proteins in six of eight examined B-cell ML cases.. The rare incidence of type II CG is characteristic of Japanese HCV+ ML patients and may influence the low incidence of low-grade B-cell ML. HCV infection may play a role in lymphomagenesis of splenic and gastric DLBCL.

Topics: Adolescent; Adult; Aged; Child; Comorbidity; Cryoglobulinemia; Epstein-Barr Virus Infections; Female; Genotype; Hepacivirus; Hepatitis B; Hepatitis C; HTLV-I Infections; Humans; Incidence; Japan; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prevalence; RNA, Viral; Viral Envelope Proteins; Viral Nonstructural Proteins

Hepatitis C virus (HCV)-associated B cell lymphomas were previously shown to express a restricted repertoire of immunoglobulin V(H) and V(L) genes, V(H)1-69 and VkappaA27, respectively. Although this suggests a role for antigen selection in the pathogenesis of these lymphomas, the driving antigen involved in the clonal expansion has not been identified. B cell response to a viral antigen, the HCV envelope glycoprotein 2 (E2), was analyzed in an asymptomatic HCV-infected patient. Single B cells, immortalized as hybridomas and selected for binding E2, were analyzed for their V gene usage. Sequences of these V region genes demonstrated that each hybridoma expressed unique V(H) and V(L) genes. Remarkably, these anti-E2 hybridomas preferentially used the V(H)1-69 gene. Analysis of replacement to silent mutation ratios indicated that the genes underwent somatic mutation and antigenic selection. In a separate report, human anti-E2 antibodies were also shown to express the same V(H) gene. These data strengthen the hypothesis that the HCV-associated lymphomas are derived from clonally expanded B cells stimulated by HCV.

Topics: Amino Acid Sequence; Clonal Deletion; DNA Mutational Analysis; Genes, Immunoglobulin; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Hybridomas; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region; Lymphoma, B-Cell; Reverse Transcriptase Polymerase Chain Reaction; Sequence Alignment; Sequence Homology, Amino Acid; Viral Envelope Proteins