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In this study, we investigated EBI3 and p28 expression in normal human B lymphocytes and in non\u2010EBV\u2010associated B\u2010cell lymphomas. Low levels of EBI3 were detected in purified tonsillar B cells and expression was upregulated upon anti\u2010CD40 or anti\u2010\u00b5 stimulation via NF\u2010\u03baB activation. In non\u2010neoplastic 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<jats:sup>+<\/jats:sup> T lymphocytes. Over 50% of EBI3<jats:sup>+<\/jats:sup> GC B cells were engaged in cell proliferation as assessed by Ki67 expression, and 10\u201330% expressed MUM1, an early marker of plasma cell differentiation expressed by late centrocytes. Many EBI3<jats:sup>+<\/jats:sup> GC B cells had downregulated bcl\u20106 expression, which further suggests that these cells correspond to late CD40\u2010activated centrocytes. Immunohistochemical analysis of 64 B\u2010cell lymphomas showed that the highest EBI3 levels were detected in follicular lymphomas and in diffuse large B\u2010cell lymphomas of both GC B\u2010cell\u2010like or non\u2010GC B\u2010cell\u2010like 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 \u00a9 2006 Pathological Society of Great Britain and Ireland. 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