Differential Eµ enhancer activity and expression of BOB.1/OBF.1, Oct2, PU.1, and immunoglobulin in reactive B‐cell populations, B‐cell non‐Hodgkin lymphomas, and Hodgkin lymphomas

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Abstract
It has previously been demonstrated that in cultured and in situ tumour cells of classical Hodgkin lymphoma (cHL), the immunoglobulin (Ig) promoter is inactive and its transcription factors Oct2 and/or BOB.1/OBF.1 are down‐regulated. In this study, the analysis of these transcription factors has been extended to a broad spectrum of B‐cell malignancies and the findings have been related to the situation in normal B‐cells of various differentiation stages and to the expression of Ig. Furthermore, an additional Ig transcription factor, PU.1, recently described to be absent from cHL, and a further regulatory element of the Ig gene, the intronic Eµ enhancer, have been studied. BOB.1/OBF.1 and Oct2 were present in all B‐cells expressing Ig, whereas PU.1 proved to be absent from late B‐cell differentiation stages and from a subset of germinal centre B‐cells. Interestingly, there were several normal (eg germinal centre centroblasts and monocytoid B‐cells) and malignant B‐cell populations (eg a proportion of diffuse large B‐cell lymphomas, DLBCLs) that were Ig‐negative, despite their BOB.1/OBF.1 and Oct2 expression. This study further shows that absence of PU.1 alone, as well as inactivation of the intronic Eµ enhancer, is not sufficient to down‐regulate Ig transcription. Taken together, the simultaneous absence of PU.1, Oct2, and/or BOB.1/OBF.1 is unique to Hodgkin and Reed–Sternberg (HRS) cells and cannot be detected in normal B‐cell subsets or B‐cell non‐Hodgkin lymphomas (B‐NHLs). This supports the concept that the down‐regulation of Ig in cHL does not reflect a physiological situation, but a defect probably closely linked to the pathogenesis of cHL. Copyright © 2004 John Wiley & Sons, Ltd.