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

• Published in: Haematologica (Roma) Vol. 108; no. 12; pp. 3347 - 3358
• Main Authors: Thurner, Lorenz, Fadle, Natalie, Regitz, Evi, Roth, Sophie, Cetin, Onur, Kos, Igor Age, Hess, Simon Mauro, Bein, Julia, Bohle, Rainer Maria, Vornanen, Martine, Sundström, Christer, De Leval, Laurence, Tiacci, Enrico, Borchmann, Peter, Engert, Andreas, Poeschel, Viola, Held, Gerhard, Schwarz, Eva C., Neumann, Frank, Preuss, Klaus-Dieter, Hoth, Markus, Küppers, Ralf, Lehman, Karola, Hansmann, Martin-Leo, Becker, Sören L., Bewarder, Moritz, Hartmann, Sylvia
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.12.2023
• Subjects: Hodgkin Disease - pathology; Humans; Lymphocytes - pathology; Micrococcaceae; Receptors, Antigen, B-Cell
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2023.282698

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.