Lymphocytes lacking I kappa B-alpha develop normally, but have selective defects in proliferation and function

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-al...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2000-11, Vol.165 (10), p.5418-5427
Main Authors: Chen, C L, Singh, N, Yull, F E, Strayhorn, D, Van Kaer, L, Kerr, L D
Format: Article
Language:English
Subjects:
Animals
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
B-Lymphocytes - pathology
Cell Differentiation - genetics
Cell Differentiation - immunology
Cell Division - genetics
Cell Division - immunology
Clone Cells
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - genetics
Epitopes, B-Lymphocyte - immunology
Fetal Tissue Transplantation - immunology
Fetal Tissue Transplantation - pathology
Fetus
Germinal Center - immunology
Germinal Center - pathology
I-kappa B Proteins
I^KB^a protein
Immunoglobulins - biosynthesis
Liver - cytology
Liver - embryology
Liver - growth & development
Liver - immunology
Liver Transplantation - immunology
Liver Transplantation - pathology
Lymphocyte Activation - genetics
Lymphocyte Subsets - cytology
Lymphocyte Subsets - immunology
Lymphocyte Subsets - metabolism
Lymphocyte Subsets - pathology
Lymphoproliferative Disorders - genetics
Lymphoproliferative Disorders - immunology
Lymphoproliferative Disorders - pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B - antagonists & inhibitors
NF-kappa B - genetics
NF-kappa B - metabolism
NF-KappaB Inhibitor alpha
Organ Specificity - genetics
Organ Specificity - immunology
Spleen - immunology
Spleen - pathology
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes - pathology
Transcriptional Activation - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.165.10.5418