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

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

doi:10.3324/haematol.2023.282698

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

Lorenz Thurner
, Natalie Fadle
, Evi Regitz
, Sophie Roth
, Onur Cetin
, Igor Age Kos
, Simon Mauro Hess
, Julia Bein
, Rainer Maria Bohle
, Martine Vornanen
, Christer Sundström
, Laurence De Leval
, Enrico Tiacci
, Peter Borchmann
, Andreas Engert
, Viola Poeschel
, Gerhard Held
, Eva C. Schwarz
, Frank Neumann
, Klaus Dieter Preuss

Markus Hoth, Ralf Küppers, Karola Lehman, Martin Leo Hansmann, Sören L. Becker, Moritz Bewarder, Sylvia Hartmann

Department of Pathology

Research output: Contribution to journal › Article › Scientific › peer-review

16 Citations (Scopus)

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Abstract

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.

Original language	English
Pages (from-to)	3347-3358
Number of pages	12
Journal	Haematologica
Volume	108
Issue number	12
DOIs	https://doi.org/10.3324/haematol.2023.282698
Publication status	Published - Dec 2023
Publication type	A1 Journal article-refereed

Publication forum classification

Publication forum level 2

ASJC Scopus subject areas

Hematology

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11074-Article Text-81040-2-10-20231129Final published version, 1.73 MBLicence: CC BY

https://urn.fi/URN:NBN:fi:tuni-202401231734Licence: CC BY

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Thurner, L., Fadle, N., Regitz, E., Roth, S., Cetin, O., Kos, I. A., Hess, S. M., Bein, J., Bohle, R. M., Vornanen, M., Sundström, C., De Leval, L., Tiacci, E., Borchmann, P., Engert, A., Poeschel, V., Held, G., Schwarz, E. C., Neumann, F., ... Hartmann, S. (2023). B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma. Haematologica, 108(12), 3347-3358. https://doi.org/10.3324/haematol.2023.282698

@article{73516eaccaa440c0b4efbf4a27169244,

title = "B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma",

abstract = "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.",

author = "Lorenz Thurner and Natalie Fadle and Evi Regitz and Sophie Roth and Onur Cetin and Kos, \{Igor Age\} and Hess, \{Simon Mauro\} and Julia Bein and Bohle, \{Rainer Maria\} and Martine Vornanen and Christer Sundstr{\"o}m and \{De Leval\}, Laurence and Enrico Tiacci and Peter Borchmann and Andreas Engert and Viola Poeschel and Gerhard Held and Schwarz, \{Eva C.\} and Frank Neumann and Preuss, \{Klaus Dieter\} and Markus Hoth and Ralf K{\"u}ppers and Karola Lehman and Hansmann, \{Martin Leo\} and Becker, \{S{\"o}ren L.\} and Moritz Bewarder and Sylvia Hartmann",

year = "2023",

month = dec,

doi = "10.3324/haematol.2023.282698",

language = "English",

volume = "108",

pages = "3347--3358",

journal = "Haematologica",

issn = "0390-6078",

publisher = "Ferrata Storti Foundation",

number = "12",

}

Thurner, L, Fadle, N, Regitz, E, Roth, S, Cetin, O, Kos, IA, Hess, SM, Bein, J, Bohle, RM, Vornanen, M, Sundström, C, De Leval, L, Tiacci, E, Borchmann, P, Engert, A, Poeschel, V, Held, G, Schwarz, EC, Neumann, F, Preuss, KD, Hoth, M, Küppers, R, Lehman, K, Hansmann, ML, Becker, SL, Bewarder, M & Hartmann, S 2023, 'B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma', Haematologica, vol. 108, no. 12, pp. 3347-3358. https://doi.org/10.3324/haematol.2023.282698

TY - JOUR

T1 - B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma

AU - Thurner, Lorenz

AU - Fadle, Natalie

AU - Regitz, Evi

AU - Roth, Sophie

AU - Cetin, Onur

AU - Kos, Igor Age

AU - Hess, Simon Mauro

AU - Bein, Julia

AU - Bohle, Rainer Maria

AU - Vornanen, Martine

AU - Sundström, Christer

AU - De Leval, Laurence

AU - Tiacci, Enrico

AU - Borchmann, Peter

AU - Engert, Andreas

AU - Poeschel, Viola

AU - Held, Gerhard

AU - Schwarz, Eva C.

AU - Neumann, Frank

AU - Preuss, Klaus Dieter

AU - Hoth, Markus

AU - Küppers, Ralf

AU - Lehman, Karola

AU - Hansmann, Martin Leo

AU - Becker, Sören L.

AU - Bewarder, Moritz

AU - Hartmann, Sylvia

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

U2 - 10.3324/haematol.2023.282698

DO - 10.3324/haematol.2023.282698

M3 - Article

C2 - 37139600

AN - SCOPUS:85173427979

SN - 0390-6078

VL - 108

SP - 3347

EP - 3358

JO - Haematologica

JF - Haematologica

IS - 12

ER -

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

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