Up-regulation of BOB.1/OBF.1 expression in normal germinal center B cells and germinal center-derived lymphomas

The BOB.1/OBF.1/OCAB.1 protein is a lymphocyte-specific transcriptional coa ctivator. It interacts with the Oct1 and Oct2 transcription factors and con tributes to the transcriptional activity of octamer moths. The analysis of established B cell Lines had suggested that BOB.1/OBF.1 is constitutively e xpressed 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, germin al center B cells show highly increased BOB.1/OBF.1 levels. We can induce t he 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 germin al center reaction due to mutations in the TNF receptor p55 or lymphotoxin beta (LT beta) receptor genes. Furthermore, we demonstrate that BOB.1/OBF.1 expression is highly regulated in human B cell lymphomas. Whereas lymphoma s representing pre- and postfollicular B cell developmental stages are nega tive for BOB.1/OBF.1, high-level expression of BOB.1/OBF.1 is characteristi c of germinal center-derived tumors. In these tumors BOB.1/OBF.1 is typical ly coexpressed with high levels of Bc16. These results imply that overexpre ssion of BOB.1/OBF.1, like overexpression of Bc16, might play a role in the pathogenesis of germinal center-derived B cell lymphomas, Furthermore, ove rexpression of BOB.1/OBF.1 represents a characteristic feature of these tum ors that is useful in their identification.