serval:BIB_77EFC721B4FE
Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma.
10.1038/s41467-020-16375-6
000536698500008
32424289
Thurner
L.
author
Hartmann
S.
author
Fadle
N.
author
Regitz
E.
author
Kemele
M.
author
Kim
Y.J.
author
Bohle
R.M.
author
Nimmesgern
A.
author
von Müller
L.
author
Kempf
VAJ
author
Weniger
M.A.
author
Neumann
F.
author
Schneider
N.
author
Vornanen
M.
author
Sundström
C.
author
de Leval
L.
author
Engert
A.
author
Eichenauer
D.A.
author
Küppers
R.
author
Preuss
K.D.
author
Hansmann
M.L.
author
Pfreundschuh
M.
author
article
2020-05-18
Nature communications
2041-1723
2041-1723
journal
11
1
2465
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 <sup>+</sup> 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 <sup>+</sup> 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 <sup>+</sup> DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD <sup>+</sup> BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies.
Adolescent
Adult
Aged
Antigens, Bacterial/immunology
Autoantigens/immunology
B-Lymphocytes/immunology
Cell Line, Tumor
Cell Proliferation
Child
DNA-Directed RNA Polymerases/metabolism
Histocompatibility Antigens Class II/metabolism
Hodgkin Disease/blood
Hodgkin Disease/immunology
Hodgkin Disease/microbiology
Humans
Immunoglobulin D/metabolism
Immunoglobulin Fab Fragments/immunology
Immunoglobulin Variable Region/genetics
Male
Middle Aged
Models, Biological
Moraxella catarrhalis/immunology
Receptors, Antigen, B-Cell/metabolism
eng
60_published
true
peer-reviewed
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
University of Lausanne
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