Variable expression of Epstein-Barr virus-induced gene 3 during normal B-cell differentiation and among B-cell lymphomas.
Epstein-Barr virus (EBV)-induced gene 3 (EBI3) is expressed by tumour cells in several EBV-associated malignancies. EBI3 was recently found to associate with a novel peptide, p28, to form a new heterodimeric cytokine, called interleukin-27. In this study, we investigated EBI3 and p28 expression in normal human B lymphocytes and in non-EBV-associated B-cell lymphomas. Low levels of EBI3 were detected in purified tonsillar B cells and expression was upregulated upon anti-CD40 or anti-micro stimulation via NF-kappaB activation. In non-neoplastic tissues, EBI3 expression by lymphocytes was largely restricted to a subset of germinal centre (GC) B cells located at the margin of the light zone, in close contact with CD3+ T lymphocytes. Over 50% of EBI3+ GC B cells were engaged in cell proliferation as assessed by Ki67 expression, and 10-30% expressed MUM1, an early marker of plasma cell differentiation expressed by late centrocytes. Many EBI3+ GC B cells had downregulated bcl-6 expression, which further suggests that these cells correspond to late CD40-activated centrocytes. Immunohistochemical analysis of 64 B-cell lymphomas showed that the highest EBI3 levels were detected in follicular lymphomas and in diffuse large B-cell lymphomas of both GC B-cell-like or non-GC B-cell-like types. No or rare p28 expression was detected in normal or tumour B cells. This constitutive expression of EBI3 by neoplastic B cells may be involved in lymphomagenesis, and may be a useful marker for lymphoma diagnosis.
Larousserie
F
F
CNRS UMR 8147, Université Paris V, Institut Fédératif de Recherche Necker, and Service d'Anatomie Pathologique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, France.
Bardel
E
E
Coulomb L'Herminé
A
A
Canioni
D
D
Brousse
N
N
Kastelein
R A
RA
Devergne
O
O
D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008224:Lymphoma, Follicular / Q000378:metabolism / Q000821:virology; D015778:Minor Histocompatibility Antigens; D014066:Palatine Tonsil / Q000821:virology; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
C097732:EBI3 protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D015778:Minor Histocompatibility Antigens; D021122:Protein Subunits; D012333:RNA, Messenger; D012334:RNA, Neoplasm