Silencing of the Expression of the Immunoglobulin Kappa Gene in Non-B Cells

Abstract

Although the activating factor NF-κB 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-κB binding sequence of the enhancer. When this fragment is added back upstream of an active NF-κB 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 C_κ locus to cells of the B lineage.