Regulation of Human Igλ Light Chain Gene Expression by NF-κB

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Abstract
The human Igλ enhancer consists of three separated sequence elements that we identified previously by mapping DNase I-hypersensitive regions (HSS) downstream of the C region of the Igλ L chain genes (HSS-1, HSS-2, and HSS-3). It has been shown by several laboratories that expression of the H chain genes as well as the κ genes, but not the λ genes, is dependent on constitutive NF-κB proteins present in the nucleus. In this study we show by band-shift experiments, in vivo footprinting, and transient transfection assays that all three hypersensitive sites of the human Igλ enhancer contain functional NF-κB sites that act synergistically on expression. We further show that the chicken λ enhancer also contains a functional NF-κB site but the mouse λ enhancer contains a mutated, nonfunctional NF-κB site that is responsible for its low enhancer activity. It is possible that the inactivating mutation in the mouse Igλ enhancer was compensated for by an expansion of the Igκ L chain locus, followed by a contraction of the Igλ locus in this species.