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Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma

Author

Listed:
  • Lorenz Thurner

    (Saarland University Medical School)

  • Sylvia Hartmann

    (Goethe University)

  • Natalie Fadle

    (Saarland University Medical School)

  • Evi Regitz

    (Saarland University Medical School)

  • Maria Kemele

    (Saarland University Medical School)

  • Yoo-Jin Kim

    (Institute of Pathology)

  • Rainer Maria Bohle

    (Institute of Pathology)

  • Anna Nimmesgern

    (University of Saarland)

  • Lutz Müller

    (Institute for Laboratory Medicine, Microbiology and Hygiene, Christophorus Kliniken)

  • Volkhard A. J. Kempf

    (University Hospital of the Goethe University)

  • Marc A. Weniger

    (Medical School
    Deutsches Konsortium für translationale Krebsforschung (DKTK))

  • Frank Neumann

    (Saarland University Medical School)

  • Nadine Schneider

    (University Hospital Frankfurt Goethe University)

  • Martine Vornanen

    (Tampere University Hospital and University of Tampere)

  • Christer Sundström

    (Uppsala University Hospital)

  • Laurence Leval

    (Lausanne University Hospital)

  • Andreas Engert

    (Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf
    First Department of Internal Medicine University Hospital Cologne)

  • Dennis A. Eichenauer

    (Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf
    First Department of Internal Medicine University Hospital Cologne)

  • Ralf Küppers

    (Medical School
    Deutsches Konsortium für translationale Krebsforschung (DKTK))

  • Klaus-Dieter Preuss

    (Saarland University Medical School)

  • Martin-Leo Hansmann

    (Goethe University
    Frankfurt am Main)

  • Michael Pfreundschuh

    (Saarland University Medical School)

Abstract

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta’ (RpoC) from Moraxella catarrhalis as frequent antigen of BCRs of IgD+ LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/κ-type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed by Moraxella catarrhalis that is known to activate IgD+ B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-κB pathway and the proliferation of IgD+ DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD+ BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies.

Suggested Citation

  • Lorenz Thurner & Sylvia Hartmann & Natalie Fadle & Evi Regitz & Maria Kemele & Yoo-Jin Kim & Rainer Maria Bohle & Anna Nimmesgern & Lutz Müller & Volkhard A. J. Kempf & Marc A. Weniger & Frank Neumann, 2020. "Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16375-6
    DOI: 10.1038/s41467-020-16375-6
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