Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma.
Lorenz ThurnerSylvia HartmannNatalie FadleEvi RegitzMaria KemeleYoo-Jin KimRainer Maria BohleAnna NimmesgernLutz von MüllerVolkhard A J KempfMarc A WenigerFrank NeumannNadine SchneiderMartine VornanenChrister SundströmLaurence de LevalAndreas EngertDennis A EichenauerRalf KüppersKlaus-Dieter PreussMartin-Leo HansmannMichael PfreundschuhPublished in: Nature communications (2020)
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.
Keyphrases
- hodgkin lymphoma
- induced apoptosis
- end stage renal disease
- cell cycle arrest
- ejection fraction
- signaling pathway
- newly diagnosed
- chronic kidney disease
- poor prognosis
- peritoneal dialysis
- gene expression
- pi k akt
- cell death
- oxidative stress
- peripheral blood
- long non coding rna
- circulating tumor
- tyrosine kinase
- genome wide analysis