ArticleHepatology communications2024
B cells expressing mutated IGHV1-69-encoded antigen receptors related to virus neutralization show lymphoma-like transcriptomes in patients with chronic HCV infection.
Article in Hepatology communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- From Antigenic Drive to Clonal Autonomy: An Update on Molecular Mechanisms of HCV-Related B-Cell Lymphomagenesis.Cancers · 2026Review
- MPXV H3L elicits broadly directed CD4 T cell responses in mpox patients and MVA vaccinees.Npj viruses · 2026Article
- Dyslipidemia-associated natural IgM improves oncolytic virus TILT-123 efficacy through antibody-dependent enhancement in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Structural and genetic signatures of two classes of HCV E2 neutralizing face antibodies from non-human primates immunized with a recombinant E1E2.NPJ vaccines · 2026Article
- Recurrent antibody repertoire features associated with six selected human IGHV genes: V(D)J usage, heavy-light pairing, and CDRH3 properties.Frontiers in immunology · 2026Article
- Chronic Hepatitis C in the Direct-Acting Antivirals Era: Carcinogenesis and Clinical Implications.Diseases (Basel, Switzerland) · 2025Review
- Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
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11 authors.
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Abstract
backgroundChronic HCV infection leads to a complex interplay with adaptive immune cells that may result in B cell dyscrasias like cryoglobulinemia or lymphoma. While direct-acting antiviral therapy has decreased the incidence of severe liver damage, its effect on extrahepatic HCV manifestations such as B cell dyscrasias is still unclear.
methodsWe sequenced B cell receptor (BCR) repertoires in patients with chronic HCV mono-infection and patients with HCV with a sustained virological response (SVR) after direct-acting antiviral therapy. This data set was mined for highly neutralizing HCV antibodies and compared to a diffuse large B cell lymphoma data set. The TKO model was used to test the signaling strength of selected B-BCRs in vitro. Single-cell RNA sequencing of chronic HCV and HCV SVR samples was performed to analyze the transcriptome of B cells with HCV-neutralizing antigen receptors.
resultsWe identified a B cell fingerprint with high richness and somatic hypermutation in patients with chronic HCV and SVR. Convergence to specific immunoglobulin genes produced high-connectivity complementarity-determining region 3 networks. In addition, we observed that IGHV1-69 CDR1 and FR3 mutations characterizing highly neutralizing HCV antibodies corresponded to recurrent point mutations found in clonotypic BCRs of high-grade lymphomas. These BCRs did not show autonomous signaling but a lower activation threshold in an in vitro cell model for the assessment of BCR signaling strength. Single-cell RNA sequencing revealed that B cells carrying these point mutations showed a persisting oncogenic transcriptome signature with dysregulation in signaling nodes such as CARD11, MALT1, RelB, MAPK, and NFAT.
conclusionsWe provide evidence that lymphoma-like cells derive from the anti-HCV immune response. In many patients, these cells persist for years after SVR and can be interpreted as a mechanistic basis for HCV-related B cell dyscrasias and increased lymphoma risk even beyond viral elimination.
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