B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1* 07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver- and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA'-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:108

Enthalten in:

Haematologica - 108(2023), 12 vom: 01. Dez., Seite 3347-3358

Sprache:

Englisch

Beteiligte Personen:

Thurner, Lorenz [VerfasserIn]
Fadle, Natalie [VerfasserIn]
Regitz, Evi [VerfasserIn]
Roth, Sophie [VerfasserIn]
Cetin, Onur [VerfasserIn]
Kos, Igor Age [VerfasserIn]
Hess, Simon Mauro [VerfasserIn]
Bein, Julia [VerfasserIn]
Bohle, Rainer Maria [VerfasserIn]
Vornanen, Martine [VerfasserIn]
Sundström, Christer [VerfasserIn]
De Leval, Laurence [VerfasserIn]
Tiacci, Enrico [VerfasserIn]
Borchmann, Peter [VerfasserIn]
Engert, Andreas [VerfasserIn]
Poeschel, Viola [VerfasserIn]
Held, Gerhard [VerfasserIn]
Schwarz, Eva C [VerfasserIn]
Neumann, Frank [VerfasserIn]
Preuss, Klaus-Dieter [VerfasserIn]
Hoth, Markus [VerfasserIn]
Küppers, Ralf [VerfasserIn]
Lehman, Karola [VerfasserIn]
Hansmann, Martin-Leo [VerfasserIn]
Becker, Sören L [VerfasserIn]
Bewarder, Moritz [VerfasserIn]
Hartmann, Sylvia [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Receptors, Antigen, B-Cell

Anmerkungen:

Date Completed 04.12.2023

Date Revised 05.12.2023

published: Electronic

Citation Status MEDLINE

doi:

10.3324/haematol.2023.282698

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM356428826