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Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma

: Thurner, L.; Hartmann, S.; Fadle, N.; Regitz, E.; Kemele, M.; Kim, Y.-J.; Bohle, R.M.; Nimmesgern, A.; Müller, L. von; Kempf, V.A.J.; Weniger, M.A.; Neumann, F.; Schneider, N.; Vornanen, M.; Sundström, C.; Leval, L. de; Engert, A.; Eichenauer, D.A.; Küppers, R.; Preuss, K.-D.; Hansmann, M.-L.; Pfreundschuh, M.

Volltext ()

Nature Communications 11 (2020), Art. 2465, 12 S.
ISSN: 2041-1723
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer IME ()

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.