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-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.
Chen
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CL
Departments of. Microbiology and Immunology and Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232. Howard Hughes Medical Institute, Chevy Chase, MD 20815. Vanderbilt-Ingram Cancer Center, Nashville, TN.
Singh
N
N
Yull
F E
FE
Strayhorn
D
D
Van Kaer
L
L
Kerr
L D
LD
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D016332:Fetal Tissue Transplantation / Q000276:immunology / Q000473:pathology; D005333:Fetus; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D020672:I-kappa B Proteins; D007136:Immunoglobulins / Q000096:biosynthesis; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation / Q000276:immunology
D004268:DNA-Binding Proteins; D018985:Epitopes, B-Lymphocyte; D020672:I-kappa B Proteins; D007136:Immunoglobulins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha