RELB IS A KEY PLAYER FOR BOTH KAPPA-D-DEPENDENT TRANSCRIPTION AND DEMETHYLATION IN B-CELLS

NF-kappa B was originally identified as a B fell-specific nuclear fact or binding to the intronic kappa-light-chain enhancer element. It is f ound constitutively in the nucleus of mature B and plasma cells. In ot her cell types including pre-B cells, NF-kappa B is sequestered in the cytoplasm but can be induced by a variety of stimuli. In contrast to essentially ail other mature B cells and plasma cell lines, the S107 p lasmacytoma cell line lacks both constitutive and inducible kappa B-bi nding activity. A molecular characterization of the defect in these S1 07 cells suggests that the primary defect lies in the signal transduct ion pathway leading to NF-kappa B induction. Ectopic expression of Rel B after stable transfection of these cells restores constitutive nucle ar kappa B-binding activity. Moreover, kappa B-dependent transcription is also restored. Finally we demonstrate, that in contrast to parenta l S107 cells, the stable RelB transfectants have also regained the abi lity to specifically demethylate a transfected immunoglobulin kappa-lo cus. These data suggest that RelB is critically involved in both B cel l-specific transcription and demethylation directed by the intronic ka ppa-enhancer element.