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(American Journal of Pathology. 2000;156:501-507.)
© 2000 American Society for Investigative Pathology

Regular Articles

Up-Regulation of BOB.1/OBF.1 Expression in Normal Germinal Center B Cells and Germinal Center-Derived Lymphomas

Axel Greiner^*, Kerstin B. Müller, Jochen Hess, Klaus Pfeffer, H. Konrad Müller-Hermelink^* and Thomas Wirth

From the Pathologisches Institut,^*
Würzburg; the Institut für Medizinische Strahlenkunde und Zellforschung,
Würzburg; and the Institut für Medizinische Mikrobiologie,
München, Germany

The BOB.1/OBF.1/OCAB.1 protein is a lymphocyte-specific transcriptional coactivator. It interacts with the Oct1 and Oct2 transcription factors and contributes to the transcriptional activity of octamer motifs. The analysis of established B cell lines had suggested that BOB.1/OBF.1 is constitutively expressed at all stages of B cell development. Here we show that expression of BOB.1/OBF.1 is regulated within the B cell lineage. Specifically, germinal center B cells show highly increased BOB.1/OBF.1 levels. We can induce the up-regulation by stimulating primary splenic B cells, eg, by triggering CD40 signaling in the presence of interleukin-4. Expression of BOB.1/OBF.1 is detectable but reduced in spleens from mice unable to undergo the germinal center reaction due to mutations in the TNF receptor p55 or lymphotoxin ß (LTß) receptor genes. Furthermore, we demonstrate that BOB.1/OBF.1 expression is highly regulated in human B cell lymphomas. Whereas lymphomas representing pre- and postfollicular B cell developmental stages are negative for BOB.1/OBF.1, high-level expression of BOB.1/OBF.1 is characteristic of germinal center-derived tumors. In these tumors BOB.1/OBF.1 is typically coexpressed with high levels of Bcl6. These results imply that overexpression of BOB.1/OBF.1, like overexpression of Bcl6, might play a role in the pathogenesis of germinal center-derived B cell lymphomas. Furthermore, overexpression of BOB.1/OBF.1 represents a characteristic feature of these tumors that is useful in their identification.

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