Activated Notch1 modulates gene expression in B cells similarly to Epstein-Barr viral nuclear antigen 2

Both Epstein-Barr viral nuclear antigen 2 (EBNA2) and activated Notch trans activate genes by interacting with the transcription factor RBP-J kappa. Th e viral protein EBNA2 may hence be regarded as a functional equivalent of a n activated Notch receptor. Until now, nothing has been known about the phy siological role of Notch signaling in B cells. Here we investigated whether activated Notch can induce the same phenotypic changes as EBNA2 in Burkitt 's lymphoma cells. An estrogen receptor fusion protein of the intracellular part of mouse Notch 1 (mNotch1-IC), mimicking in the presence of estrogen a constitutively active Notch receptor, was stably transfected into the Bur kitt's lymphoma cell lines BL41-P3HR1 and HH514. Northern blot analysis rev ealed that the LMP2A gene is induced by Notch-IC in the presence of estroge n, whereas increased expression of LMP1 could be detected only if cyclohexi mide was simultaneously added. Concerning the cellular genes regulated by E BNA2, Notch-IC was able to upregulate CD21 but not CD23 expression. Immunog lobulin mu (Ig mu) expression, which is downregulated by EBNA2, was also ne gatively regulated by Notch-IC. Similarly to EBNA2, Notch-IC was able to re press c-myc expression, which is under the control of the immunoglobulin he avy-chain locus in Burkitt's lymphoma cells with a t(8;14) translocation. T he data show that Notch-IC is able to participate in gene regulation in B c ells.