Identification and localization of an enhancer for the human lambda L chain Ig gene complex.

Abstract

A strong transcriptional enhancer was identified for the human lambda L chain Ig gene complex. Enhancer activity was measured by activation of the chloramphenicol acetyl transferase (CAT) gene in a transient assay using both mouse and human B lymphoid cell lines. The smallest fragment identified with enhancer activity was 111 bp, which resides 11.7 kb downstream (3') of C lambda 7, a constant region gene we have recently isolated and identified as functional in the human population. Enhancer activity is orientation independent, tissue specific (active in all B cell lines tested and not in a T cell line), and independent of NF kappa B, similar to the mouse lambda enhancers recently reported. The human lambda enhancer is active in both mouse and human B cell lines; interestingly, the mouse lambda enhancers are active in mouse lines but not in a human B cell line. DNA sequence comparison of the mouse and human lambda enhancers indicates a higher degree of homology (average of 72.5%) within the 111-bp enhancer core region identified here than for the remaining flanking sequence compared (average of 42%). This discovery of an enhancer in the human lambda locus (HuE lambda), which is clearly distinct from that of the H and L chain loci, will help to determine the mechanism for the ordered expression and rearrangement of these gene complexes in B cell ontogeny. The presence of only one enhancer in the human C lambda complex 3' of all the C genes suggests that the evolutionary duplication of the L locus differs from that seen in mouse; in mouse the duplication unit was JCJC-enhancer, whereas the human JC lambda s duplicated without the enhancer.