NEGATIVE REGULATION OF IMMUNOGLOBULIN-KAPPA LIGHT-CHAIN GENE-TRANSCRIPTION BY A SHORT SEQUENCE HOMOLOGOUS TO THE MURINE B1 REPETITIVE ELEMENT

B-cell-specific expression of the immunoglobulin kappa light-chain (Igkappa) gene is in part accomplished by negative regulatory influences. Here we describe a new negatively acting element (termed kappaNE) immediately upstream of the NF-kappaB-binding site in the Igkappa intronic enhancer. The 27-bp kappaNE sequence is conserved in the corresponding positions in the rabbit and human Igkappa genes, and the human kappaNE homolog was shown to have a similar negative regulatory activity. Data base searches using the mouse kappaNE sequence revealed a striking homology to murine B1 repetitive sequences. A sequence homologous to kappaNE and B1 was also noted in a previously identified silencer element in the murine T-cell receptor of locus. The homologous T-cell receptor alpha locus sequence, but notably not a corresponding 27-bp BI consensus sequence, showed a negative regulatory potential similar to that Of kappaNE. The negative effect of kappaNE by itself was not cell type specific but became so when paired with its 5'-flanking sequence in the Igkappa enhancer. A short (30-bp) fragment upstream of kappaNE (termed kappaBS) was found to be necessary and sufficient for abolishing the negative effect of kappaNE in B cells. Point mutations in a T-rich motif within the kappaBS sequence allowed the transcriptional repression by kappaNE to be evident in B cells as well as other cells. As suggested by this cell-independent negative activity, proteins binding to the mouse and human kappaNE sequences were identified in all cell types tested.