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

• Published in: Nature communications Vol. 11; no. 1; pp. 2465 - 12
• Main Authors: Thurner, Lorenz, Hartmann, Sylvia, Fadle, Natalie, Regitz, Evi, Kemele, Maria, Kim, Yoo-Jin, Bohle, Rainer Maria, Nimmesgern, Anna, von Müller, Lutz, Kempf, Volkhard A. J., Weniger, Marc A., Neumann, Frank, Schneider, Nadine, Vornanen, Martine, Sundström, Christer, de Leval, Laurence, Engert, Andreas, Eichenauer, Dennis A., Küppers, Ralf, Preuss, Klaus-Dieter, Hansmann, Martin-Leo, Pfreundschuh, Michael
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.05.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/51; 631/250/2499; 631/250/2520; 692/4028/67; 82/1; 82/47; 82/58; 82/79; 82/80; Adolescent; Adult; Aged; Antibodies; Antigens; Antigens, Bacterial - immunology; Autoantigens - immunology; B-cell receptor; B-Lymphocytes - immunology; Cell Line, Tumor; Cell Proliferation; Child; Cloning; Deoxyribonucleic acid; DNA; DNA-directed RNA polymerase; DNA-Directed RNA Polymerases - metabolism; Drb1 protein; Histocompatibility antigen HLA; Histocompatibility Antigens Class II - metabolism; Hodgkin Disease - blood; Hodgkin Disease - immunology; Hodgkin Disease - microbiology; Hodgkin's lymphoma; Humanities and Social Sciences; Humans; Immunoglobulin D; Immunoglobulin D - metabolism; Immunoglobulin Fab Fragments - immunology; Immunoglobulin G; Immunoglobulin Variable Region - genetics; Lymphocytes; Lymphocytes B; Lymphoma; Major histocompatibility complex; Male; Middle Aged; Models, Biological; Moraxella catarrhalis; Moraxella catarrhalis - immunology; multidisciplinary; NF-κB protein; Patients; Receptors; Receptors, Antigen, B-Cell - metabolism; RNA polymerase; Science; Science (multidisciplinary); Stimulation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16375-6

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. Nodular lymphocyte-predominant Hodgkin lymphoma with IgD+ lymphocyte-predominant (LP) cells is a rare clinical distinct lymphoma subset of B-cell origin. Here the authors show that antigens expressed by Moraxella catarrhalis are recognized by B cell receptors of IgD+ LP cells, suggesting the contribution of chronic antigen stimulation to lymphomagenesis.