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Lymphoma

Immunoglobulin gene repertoire in ocular adnexal lymphomas: hints on the nature of the antigenic stimulation

Leukemia volume 26, pages 814–821 (2012)Cite this article

Abstract

Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40% Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11%) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells.

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Acknowledgements

This work was in part supported by Associazione Italiana per la Ricerca sul Cancro (AIRC, Milan, to PG and RD), Progetti di Ricerca di Interesse Nazionale (PRIN), Progetto Integrato Oncologia (PIO), Fondazione CARIPLO, Milan; and the ENosAI project (code 09SYN-13-880), co-funded by the EU and the Hellenic General Secretariat for Research and Technology (to KS). Elisa Pasini is a fellow of the Fondazione Italiana per la Ricerca sul Cancro (FIRC).

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Authors and Affiliations

  1. Division of Molecular Oncology, Laboratory of B-cell Neoplasia, San Raffaele Scientific Institute, Milan, Italy

    A Dagklis & P Ghia

  2. Università Vita-Salute San Raffaele, Milan, Italy

    A Dagklis & P Ghia

  3. MAGIC (Microenvironment and Genes in Cancers of the Blood) Interdivisional Research Program, Istituto Scientifico San Raffaele, Milan, Italy

    A Dagklis, M Ponzoni, S Govi, M G Cangi, A Vino, C Doglioni, A J M Ferreri & P Ghia

  4. Unit of Lymphoid Malignances, Pathology Unit, San Raffaele Scientific Institute, Milan, Italy

    M Ponzoni, M G Cangi, A Vino & C Doglioni

  5. Department of Oncology, Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy

    M Ponzoni, S Govi, A Vino, C Doglioni, A J M Ferreri & P Ghia

  6. Cancer Bio-Immunotherapy Unit, CRO – National Cancer Institute, Aviano, Italy

    E Pasini & R Dolcetti

  7. Department of Pathology and Université Pierre et Marie Curie, Hôpital Pitié-Salpètrière, Paris, France

    F Charlotte

  8. Laboratory of Hematology and Université Pierre et Marie Curie, Hôpital Pitié-Salpètrière, Paris, France

    F Davì

  9. Department of Medicine, Division of Hematology, Oncology, and Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

    I S Lossos

  10. 1st Department of Ophthalmology, Henri Dunant Hospital, Athens, Greece

    I Ntountas

  11. Hematopathology Department, Evangelismos Hospital, Athens, Greece

    T Papadaki

  12. Hematology Department and HCT Unit, G Papanicolaou Hospital, Thessaloniki, Greece

    K Stamatopoulos

  13. Institute of Agrobiotechnology, Center for Research and Technology, Thessaloniki, Greece

    K Stamatopoulos

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  1. A Dagklis
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Correspondence to M Ponzoni.

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Dagklis, A., Ponzoni, M., Govi, S. et al. Immunoglobulin gene repertoire in ocular adnexal lymphomas: hints on the nature of the antigenic stimulation. Leukemia 26, 814–821 (2012). https://doi.org/10.1038/leu.2011.276

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  • DOI: https://doi.org/10.1038/leu.2011.276

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