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 von Müller, Volkhard A.J. Kempf, Marc A. Weniger, Frank Neumann, Nadine Schneider, Martine Vornanen, Christer Sundström, Laurence de Leval, Andreas Engert, Dennis A. Eichenauer, Ralf Küppers, Klaus Dieter PreussMartin Leo Hansmann, Michael Pfreundschuh

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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.

Original languageEnglish
Article number2465
JournalNature Communications
Volume11
DOIs
Publication statusPublished - 2020
Publication typeA1 Journal article-refereed

Publication forum classification

  • Publication forum level 3

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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