Abstract
NF-kappaB has been implicated in the development, activation, and function of B and T lymphocytes. We have evaluated the in vivo effects of deletion of IkappaB-alpha, a major inhibitor of NF-kappaB, on lymphocyte development, proliferation, and function. To elucidate the long term role of IkappaB-alpha in lymphocytes, fetal liver cells of 14.5-day-old IkappaB-alpha(-/-) or wild-type embryos were transplanted into irradiated recombinase-activating gene-2-deficient mice. Within 4 wk, the IkappaB-alpha(-/-) fetal liver cells reconstitute mature B and T cell populations in the recipients comparable to those produced by wild-type fetal liver cells. However, the proliferative responses of IkappaB-alpha(-/-) B cells are enhanced, whereas those of IkappaB-alpha(-/-) T cells are reduced. The levels of IgG1, IgG2a, IgA, and IgE produced by IkappaB-alpha(-/-) B cells are elevated relative to those produced by IkappaB-alpha(+/+) or IkappaB-alpha(+/-). Moreover, the specific immune responses to OVA and the generation of germinal centers are impaired in recipients of IkappaB-alpha(-/-) fetal liver cells. These results indicate that IkappaB-alpha plays a vital role in signal transduction pathways regulating lymphocyte proliferation and also in the production of specific Ig isotypes.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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B-Lymphocytes / pathology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Division / genetics
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Cell Division / immunology
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Clone Cells
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DNA-Binding Proteins / deficiency*
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DNA-Binding Proteins / genetics*
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Epitopes, B-Lymphocyte / immunology
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Fetal Tissue Transplantation / immunology
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Fetal Tissue Transplantation / pathology
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Fetus
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Germinal Center / immunology
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Germinal Center / pathology
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I-kappa B Proteins*
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Immunoglobulins / biosynthesis
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Liver / cytology
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Liver / embryology
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Liver / growth & development
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Liver / immunology
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Liver Transplantation / immunology
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Liver Transplantation / pathology
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Lymphocyte Activation / genetics*
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Lymphocyte Subsets / cytology
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Lymphocyte Subsets / immunology*
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Lymphocyte Subsets / metabolism*
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Lymphocyte Subsets / pathology
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Lymphoproliferative Disorders / genetics*
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Lymphoproliferative Disorders / immunology
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Lymphoproliferative Disorders / pathology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Organ Specificity / genetics
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Organ Specificity / immunology
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Spleen / immunology
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Spleen / pathology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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Transcriptional Activation / immunology
Substances
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DNA-Binding Proteins
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Epitopes, B-Lymphocyte
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I-kappa B Proteins
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Immunoglobulins
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NF-kappa B
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Nfkbia protein, mouse
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NF-KappaB Inhibitor alpha