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A stereotyped light chain may shape virus-specific B-cell receptors in HCV-dependent lymphoproliferative disorders

Genes & Immunity volume 21, pages 131–135 (2020)Cite this article

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Abstract

Hepatitis C virus (HCV) causes B-cell lymphoproliferative disorders (LPDs) expressing stereotyped B-cell receptors (BCRs) endowed with rheumatoid factor (RF) activity and putatively recognizing the HCV E2 protein. To further untangle the shaping and function of these BCRs, we analyzed immunoglobulin gene rearrangements of monoclonal B cells from 13 patients with HCV-associated LPDs and correlated their features with the clinical outcomes of antiviral therapy. While only two patients shared a stereotyped heavy-chain complementarity determining region 3 (CDR3) sequence, two kappa chain CDR3 stereotyped sequences accounted for 77% of BCRs. Light chains were enriched in sequences homologous to anti-HCV E2 antibodies compared with heavy chains (7/13 vs. 0/13; p = 0.005). Anti-HCV E2 homology was uniquely associated (7/7 vs. 0/6; p = 0.0006) with a stereotyped CDR3 sequence encoded by IGKV3-20/3D-20 gene(s) accounting for 54% of BCRs. An IGKV3-15/IGKJ1-encoded stereotyped sequence homologous to WA RF accounted for 23% of BCRs. LPDs expressing KCDR3s homologous to anti-HCV E2 antibodies responded more frequently to the eradication of HCV by antiviral therapy (6/6 vs. 1/6; p = 0.015). These findings, although limited by the small sample size, suggest that a stereotyped KCDR3 may predominantly shape anti-HCV specificity of BCRs, possibly providing a signature that may help identifying bona fide HCV-dependent LPDs.

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Fig. 1: CDR3 motifs in heavy and light chains of patients with HCV-related LPDs.

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Acknowledgements

The authors thank Veronica Morea for critically revising the analysis of sequences.

Funding

This work was supported in part by the Istituto Pasteur Italia-Fondazione Cenci Bolognetti (grant number 2017-76 to MV) and by the Intramural Research Program of Sapienza University of Rome (grant number RM11715C7D005D19 to MC).

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Authors and Affiliations

  1. Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy

    Ylenia A. Minafò

  2. Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

    Ylenia A. Minafò, Martina Del Padre, Stefania Colantuono, Alessandro Pulsoni, Milvia Casato, Massimo Fiorilli & Marcella Visentini

  3. Istituto Dermopatico dell’Immacolata, IDI-IRCCS, Rome, Italy

    Cristina Cristofoletti, Elisabetta Caprini & Marie Perez

  4. Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden

    Alaitz Aranburu

  5. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Laura Gragnani & Anna Linda Zignego

  6. Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy

    Arianna Di Napoli

  7. Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome, Italy

    Marcella Visentini

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  1. Ylenia A. Minafò
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Correspondence to Marcella Visentini.

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Minafò, Y.A., Del Padre, M., Cristofoletti, C. et al. A stereotyped light chain may shape virus-specific B-cell receptors in HCV-dependent lymphoproliferative disorders. Genes Immun 21, 131–135 (2020). https://doi.org/10.1038/s41435-020-0093-9

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