6533b7d3fe1ef96bd1261528

RESEARCH PRODUCT

Follicular dendritic cells display microvesicle-associated LMP1 in reactive germinal centers of EBV+ classic Hodgkin lymphoma

Stefania UcciniGiuseppina PepeMazin Faisal Al-jadiryArianna Di NapoliSalma Abbas Al-hadadClaudio TripodoAnna PasquiniAdel R. AlsaadawiLuigi Ruco

subject

0301 basic medicineMaleEpstein-Barr Virus InfectionsClassic Hodgkin lymphoma (cHL)CD30Follicular dendritic cells (FDCs)Exosomes and&nbsp0302 clinical medicineclassic hodgkin lymphoma (chl); epstein-barr virus (ebv); exosomes and microvesicles; follicular dendritic cells (fdcs); latent membrane protein-1 (lmp1); programmed death ligand 1 (pd-l1)Nodular sclerosisCell-Derived MicroparticlesEpstein-Barr Virus Infectionhemic and lymphatic diseasesChildCD63MicrovesicleGeneral MedicineMiddle AgedHodgkin DiseaseEpstein-Barr virus (EBV)Cell-Derived Microparticle030220 oncology & carcinogenesisProgrammed death ligand 1 (PD-L1)microvesicleOriginal ArticleFemaleHumanAdultBiologyVirusPathology and Forensic MedicineViral Matrix Proteins03 medical and health sciencesExosomes and microvesiclesmedicineotorhinolaryngologic diseasesHumansMolecular BiologyEpstein–Barr virus infectionAgedFollicular dendritic cellsGerminal centerCell Biologymedicine.diseaseGerminal CenterMolecular biologystomatognathic diseases030104 developmental biologyLatent membrane protein-1 (LMP1)Dendritic Cells Follicular

description

Expression of the latent membrane protein-1 (LMP1) of Epstein-Barr virus (EBV) was investigated in 153 cases of EBV+ classic Hodgkin lymphoma (cHL); 120 cases were pediatric patients (< 14 years of age) from Iraq, and 33 cases were adult patients from Italy. We describe for the first time the presence of LMP1 protein in EBV-encoded RNA (EBER)-negative follicular dendritic cells (FDCs) of reactive germinal centers (GC) associated with EBV+ cHL. Presence of LMP1+ GCs was independent of geographic region and age of patients. Variable numbers of reactive GCs were present in 22.2% of cases (34 of 153), whereas LMP1 staining of FDCs was present in about a third of cases (10 of 34) with reactive GC. Most cases with LMP1+ GC were mixed-cellularity (MC) subtype, but some nodular sclerosis (NS) was also present. GC cells with LMP1+ FDCs were surrounded by numerous EBV-infected cells which were positive for EBER, LMP1, and CD30. Double immunolocalization analysis revealed that LMP1 was associated with CD63, an exosomal marker, and with CD21. The possibility is discussed that peri-follicular EBV-infected cells release LMP1 protein, perhaps through exosomes, and that the protein is then captured by FDCs and is presented to EBER-negative GC B cells.

10.1007/s00428-019-02605-whttp://hdl.handle.net/10447/395031