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Lymphoma

Chlamydophila psittaci-negative ocular adnexal marginal zone lymphomas express self polyreactive B-cell receptors

Leukemia volume 29, pages 1587–1599 (2015)Cite this article

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Abstract

The pathogenesis of Chlamydophila psittaci-negative ocular adnexal extranodal marginal zone lymphomas (OAEMZLs) is poorly understood. OAEMZLs are monoclonal tumors expressing a biased repertoire of mutated surface immunoglobulins. Antigenic activation of the B-cell receptor (BCR) may have a role in the pathogenesis of these lymphomas. We have analyzed the reactivity of recombinant OAEMZL immunoglobulins. OAEMZL antibodies reacted with self-human antigens, as demonstrated by enzyme-linked immunosorbent assays, HEp-2 immunofluorescence and human protein microarrays. All the analyzed recombinant antibodies (rAbs) exhibited polyreactivity by comprehensive protein array antibody reactivity and some rAbs also demonstrated rheumatoid factor activity. The identity of several reactive antigens was confirmed by microcapillary reverse-phase high-performance liquid chromatography nano-electrospray tandem mass spectrometry. The tested rAbs frequently reacted with shared intracellular and extracellular self-antigens (for example, galectin-3). Furthermore, these self-antigens induced BCR signaling in B cells expressing cognate surface immunoglobulins derived from OAEMZLs. These findings indicate that interactions between self-antigens and cognate OAEMZL tumor-derived BCRs are functional, inducing intracellular signaling. Overall, our findings suggest that self-antigen-induced BCR stimulation may be implicated in the pathogenesis of C. psittaci-negative OAEMZLs.

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Acknowledgements

ISL is supported by National Institutes of Health (NIH) grant NIH CA109335, the Lymphoma Research Foundation and the Dwoskin Family, Recio Family, Greg Olsen and Anthony Rizzo Family Foundations.

Author Contributions

DZ and SB performed most of the laboratory work, analyzed the data and wrote the manuscript; XL and FG performed the laboratory experiments; HV analyzed the data; DKH and F-TL provided the reagents and useful discussion; and SAC, KK and FV performed the double immunofluorescence experiments. JRC-F performed the laboratory experiments and analyzed the data; ISL conceptualized the idea of the study, supervised the experiments, analyzed the data and wrote the manuscript.

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Author notes

  1. D Zhu and S Bhatt: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA

    D Zhu, S Bhatt, X Lu, F Guo & I S Lossos

  2. Department of Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

    S Bhatt & I S Lossos

  3. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    H Veelken

  4. Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, CA, USA

    D K Hsu & F-T Liu

  5. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC

    F-T Liu

  6. Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan

    F-T Liu

  7. Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA

    S Alvarez Cubela

  8. Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, USA

    K Kunkalla, F Vega & J R Chapman-Fredricks

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Correspondence to I S Lossos.

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Zhu, D., Bhatt, S., Lu, X. et al. Chlamydophila psittaci-negative ocular adnexal marginal zone lymphomas express self polyreactive B-cell receptors. Leukemia 29, 1587–1599 (2015). https://doi.org/10.1038/leu.2015.39

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