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‐µ stimulation via NF‐κB 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. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.