NF-kappa B RelA-deficient lymphocytes: normal development of T cells and B cells, impaired production of IgA and IgG1 and reduced proliferative responses.
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.
Doi
T S
TS
Laboratory of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Takahashi
T
T
Taguchi
O
O
Azuma
T
T
Obata
Y
Y
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D017690:Cell Transplantation; D016332:Fetal Tissue Transplantation; D005804:Genes, Lethal; D006579:Heterozygote; D006720:Homozygote; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D007376:Interleukin-2 / Q000096:biosynthesis; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D016328:NF-kappa B / Q000172:deficiency* / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology; D051996:Transcription Factor RelA
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007376:Interleukin-2; D016328:NF-kappa B; D015375:Receptors, Interleukin-2; D051996:Transcription Factor RelA