Regulation of human Ig lambda light chain gene expression by NF-kappa B

The human Iglambda 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 Iglambda L chain genes (HSS-1, HSS-2, and HSS-3). It has been shown by several laboratories that expression of the...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-02, Vol.168 (3), p.1259-1266
Main Authors: Combriato, Gabriele, Klobeck, H Gustav
Format: Article
Language:English
Subjects:
Animals
B-Lymphocytes - cytology
B-Lymphocytes - metabolism
Binding Sites - genetics
Binding Sites - immunology
Cell Differentiation - genetics
Cell Differentiation - immunology
Chickens
Deoxyribonuclease I - genetics
Deoxyribonuclease I - metabolism
Enhancer Elements, Genetic - immunology
Gene Expression Regulation, Neoplastic - immunology
Genes, Immunoglobulin
Humans
Immunoglobulin lambda-Chains - biosynthesis
Immunoglobulin lambda-Chains - genetics
Mice
Mice, Inbred C57BL
NF-kappa B - biosynthesis
NF-kappa B - genetics
NF-kappa B - physiology
Point Mutation
Transcription, Genetic - immunology
Transfection
Tumor Cells, Cultured
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Summary:The human Iglambda 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 Iglambda 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 kappa genes, but not the lambda genes, is dependent on constitutive NF-kappaB 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 Iglambda enhancer contain functional NF-kappaB sites that act synergistically on expression. We further show that the chicken lambda enhancer also contains a functional NF-kappaB site but the mouse lambda enhancer contains a mutated, nonfunctional NF-kappaB site that is responsible for its low enhancer activity. It is possible that the inactivating mutation in the mouse Iglambda enhancer was compensated for by an expansion of the Igkappa L chain locus, followed by a contraction of the Iglambda locus in this species.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.168.3.1259