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PMID: 9120401 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

NF-kappa B RelA-deficient lymphocytes: normal development of T cells and B cells, impaired production of IgA and IgG1 and reduced proliferative responses.

The Journal of experimental medicine ·Vol. 185 ·No. 5 ·1997-03-03 ·Pages 953-61

Doi TS, Takahashi T, Taguchi O, Azuma T, Obata Y

Abstract

To investigate the function of NF-kappa B RelA (p65), we generated mice deficient in this NF-kappa B family member by homologous recombination. Mice lacking RelA showed liver degeneration and died around embryonic day 14.5. To elucidate the role of RelA in lymphocyte development and function, we transplanted fetal liver cells of 13.5-day embryos from heterozygote matings into irradiated SCID mice. Within 4 weeks, both T and B cells had developed in the SCID mice receiving relA-/- fetal liver transplants, similar to the relA+/+ and +/- cases. T cells were found to mature to Thy-1+/TCR alpha beta +/CD3+/CD4+ or CD8+, while B cells had the ability to differentiate to IgM+/B220+ and to secrete immunoglobulins. However, the secretion of IgG1 and IgA was reduced in RelA-deficient B cells. Furthermore, both T and B cells lacking RelA showed marked reduction in proliferative responses to stimulation with Con A, anti-CD3, anti-CD3 + anti-CD28, LPS, anti-IgM, and PMA + calcium ionophore. The results indicate that RelA plays a critical role in production of specific Ig isotypes and also in signal transduction pathways for lymphocyte proliferation.

MeSH Terms
Animals B-Lymphocytes/immunology Cell Transplantation Fetal Tissue Transplantation Genes, Lethal Heterozygote Homozygote Immunoglobulin A/blood Immunoglobulin G/blood Interleukin-2/biosynthesis Liver Transplantation Lymphocyte Activation Lymphocytes/immunology Mice Mice, Inbred C57BL Mice, Mutant Strains Mice, SCID NF-kappa B/deficiency,genetics Receptors, Interleukin-2/biosynthesis T-Lymphocytes/immunology Transcription Factor RelA
Chemicals
Immunoglobulin A Immunoglobulin G Interleukin-2 NF-kappa B Receptors, Interleukin-2 Transcription Factor RelA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Doi T S
Laboratory of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Takahashi T
Taguchi O
Azuma T
Obata Y
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.185.5.953
Published
1997-03-03
Pages
953-61
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196168
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.185.5.953 PMC Full Text View journal details
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