Thurner, Lorenz, Hartmann, Sylvia, Fadle, Natalie, Regitz, Evi, Kemele, Maria, Kim, Yoo-Jin, Bohle, Rainer Maria, Nimmesgern, Anna, von Mueller, Lutz, Kempf, Volkhard A. J., Weniger, Marc A., Neumann, Frank, Schneider, Nadine, Vornanen, Martine, Sundstrom, Christer, de Leval, Laurence, Engert, Andreas, Eichenauer, Dennis A., Kueppers, Ralf, Preuss, Klaus-Dieter, Hansmann, Martin-Leo and Pfreundschuh, Michael (2020). Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma. Nat. Commun., 11 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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/kappa -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-kappa B 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. Nodular lymphocyte-predominant Hodgkin lymphoma with IgD+ lymphocyte-predominant (LP) cells is a rare clinical distinct lymphoma subset of B-cell origin. Here the authors show that antigens expressed by Moraxella catarrhalis are recognized by B cell receptors of IgD+ LP cells, suggesting the contribution of chronic antigen stimulation to lymphomagenesis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Thurner, LorenzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, SylviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fadle, NatalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Regitz, EviUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kemele, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kim, Yoo-JinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bohle, Rainer MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nimmesgern, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Mueller, LutzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kempf, Volkhard A. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weniger, Marc A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumann, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vornanen, MartineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sundstrom, ChristerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Leval, LaurenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engert, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eichenauer, Dennis A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kueppers, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preuss, Klaus-DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansmann, Martin-LeoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfreundschuh, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-333513
DOI: 10.1038/s41467-020-16375-6
Journal or Publication Title: Nat. Commun.
Volume: 11
Number: 1
Date: 2020
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CYTIDINE DEAMINASE AID; MALT LYMPHOMA; OPEN-LABEL; H CELLS; EXPRESSION; DISEASE; PROTEIN; ACTIVATION; ORIGIN; RECEPTORSMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33351

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