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

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, Nadine Schneider, Martine Vornanen, Christer Sundström, Laurence Leval, Andreas Engert, Dennis A. Eichenauer, Ralf Küppers, Klaus-Dieter Preuss, Martin-Leo Hansmann and Michael Pfreundschuh
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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
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
Dennis A. Eichenauer: Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf
Ralf Küppers: Medical School
Klaus-Dieter Preuss: Saarland University Medical School
Martin-Leo Hansmann: Goethe University
Michael Pfreundschuh: Saarland University Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16375-6

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