Although the activating factor NF-cB can be present in the nucleus of many cell types, transcription and rearrangement of the immunoglobulin kappa chain gene is restricted to cells of the B lineage. Part of this specificity is determined by sequences within the major intron of the kappa gene that specifically silence gene expression in non-B cells (T cells and HeLa cells). These sequences are found in a 232-bp fragment located 5' of the NF-KB binding sequence of the enhancer. When this fragment is added back upstream of an active NF-KB site, it specifically decreases the expression of a linked gene by more than 10-fold in activated T cells but it has no effect on expression in B cells. The kappa silencer region acts in an orientation-and distanceindependent manner and appears to be composed of multiple negative elements. The kappa silencer may act to restrict transcription and rearrangement of the CK locus to cells of the B lineage.The immunoglobulin kappa chain gene is under precise developmental control. This gene is expressed only in cells of the B-lymphocyte lineage. The transcription of the murine kappa locus is regulated by the binding of nuclear factors to DNA sequences within the V,< promoters and the two enhancer regions, one located within the J-C,K intron and another located downstream of the CK coding region (5,13,15,32,40,42). Several regulatory sequences within the intron enhancer are important for enhancer function in B cells (14,27,46). These include the E motifs (KE1, KE2, and KE3), which are homologous to the protein-binding consensus sequence CAGGTGGC in the immunoglobulin heavychain enhancer and the kB site, GGGACTTTCC, which binds the nuclear factor NF-KB (46). The activation of both CK transcription and rearrangement occurs at the pre-B-to B-cell transition and is correlated with the induction of NF-KB (37,39,47,51 including interleukin-2 receptor alpha chain (7). Significantly, NF-KB can also activate several viral enhancers, including the human immunodeficiency virus enhancer, the simian virus 40 enhancer, and the cytomegalovirus enhancer (8,33).Since NF-KB can stimulate so many different genes in T and B cells, it is clear that NF-KB by itself cannot account for the precise tissue-specific regulation of each of these genes. There must be additional regulatory elements which modify the activity of NF-KB and prevent the inappropriate activation of all these genes at once. We and others have previously observed that the NF-KB binding sequence alone can activate transcription in either B cells or non-B cells treated with PMA (36,41,56