TY - JOUR
T1 - Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma
AU - Thurner, Lorenz
AU - Hartmann, Sylvia
AU - Fadle, Natalie
AU - Regitz, Evi
AU - Kemele, Maria
AU - Kim, Yoo Jin
AU - Bohle, Rainer Maria
AU - Nimmesgern, Anna
AU - von Müller, Lutz
AU - Kempf, Volkhard A.J.
AU - Weniger, Marc A.
AU - Neumann, Frank
AU - Schneider, Nadine
AU - Vornanen, Martine
AU - Sundström, Christer
AU - de Leval, Laurence
AU - Engert, Andreas
AU - Eichenauer, Dennis A.
AU - Küppers, Ralf
AU - Preuss, Klaus Dieter
AU - Hansmann, Martin Leo
AU - Pfreundschuh, Michael
N1 - Funding Information:
This article is dedicated to the memory of M. Pfreundschuh, who died during its preparation. We are grateful to Patricia Flüchter, Sabine Albrecht, Ralf Lieberz, and Wibke Ballhorn for technical assistance. We thank Gabi Carbon, Claudia Schormann, Moritz Bewarder, and the DSHNHL team, Karola Lehmann, Andreas Meinke, Gerhard Held, Norbert Graf, and Bernhard Thurner for constant support, advice, and critical reading of the manuscript. Sources of Funding: M.P., L.T. K.-D.P., and F.N. have been supported by the Wilhelm Sander Stiftung. L.T. was supported by a University of Saarland fellowship. S.H. is supported by the Deutsche Forschungsgemeinschaft (grant HA 6145/3-1). V.A.J.K. was supported by the Viral and Bacterial Adhesin Network Training (ViBrANT) Program funded by the European Union’s HORIZON 2020 Research and Innovation Program under the Marie Sklodowska-Curie Grant Agreement No. 765042, by the Deutsche Forschungsgemeinschaft [DFG FOR 2251] and by the Robert Koch-Institute, Berlin, Germany (Bartonella consiliary laboratory, 1369-354).
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-020-16375-6
DO - 10.1038/s41467-020-16375-6
M3 - Article
C2 - 32424289
AN - SCOPUS:85084785638
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2465
ER -