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

Doi TS, Takahashi T, Taguchi O, Azuma T, Obata Y - J. Exp. Med. (1997)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.

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.

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Related in: MedlinePlus

Surface antigen profiles of spleen cells and thymocytes of  SCID mice transplanted with ED13.5 fetal liver cells. Cells were examined by two-color staining using various combinations of antibodies. The  expression of H-2Kb by spleen cells confirms their fetal liver origin. As for  T cell markers, Thy-1, TCRαβ, CD3, CD4, and CD8 were examined  and as for B cell makers, IgM and B220 were examined. Even relA−/−  fetal liver cells develop normally to mature T and B cells in the transplanted SCID mice.
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Figure 5: Surface antigen profiles of spleen cells and thymocytes of SCID mice transplanted with ED13.5 fetal liver cells. Cells were examined by two-color staining using various combinations of antibodies. The expression of H-2Kb by spleen cells confirms their fetal liver origin. As for T cell markers, Thy-1, TCRαβ, CD3, CD4, and CD8 were examined and as for B cell makers, IgM and B220 were examined. Even relA−/− fetal liver cells develop normally to mature T and B cells in the transplanted SCID mice.

Mentions: To test whether RelA-deficient stem cells can differentiate into T and B cells, the cell surface markers on lymphocytes of transplanted mice were examined. As shown in Fig. 5, the relA−/− hematopoietic stem cells differentiated to Thy1+/TCRαβ+ /CD3+/CD4+ or CD8+ T cells and IgM+/ B220+ B cells in the periphery, similarly to the relA+/+ and +/− stem cells. In addition, testing of the expression of activation markers of T cells, IL-2Rα (CD25) and CD44 (Pgp-1), revealed 6.6 and 2.5% of relA−/− spleen cells to be positive, respectively, with no significant differences from the relA+/+ or +/− cases (data not shown). The results with cells in lymph nodes were essentially identical to those of spleens (data not shown). The relA−/− thymuses with much fewer cells than those of relA+/+ and +/−, showed reduction of the CD4+/CD8+ immature population, which may have been caused by the absence of RelA. Altogether, these results suggested that RelA is not necessary for the maturation of lymphocytes or that the loss of RelA function can be compensated for by other members of the NF-κB family. In this regard, it was interesting to note that none of the mice deficient in any NF-κB subunit, whether RelA, c-Rel, RelB, or p50, showed abnormality in the development of T cells and B cells. There is a vast amount of evidence indicating the importance of NF-κB in lymphocyte development (for review see references 1, 3, 37). Thus, it is most likely that the development of T and B cells proceeds with certain combinations of NF-κB subunits and may not require the presence of specific NF-κB dimers.


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

Doi TS, Takahashi T, Taguchi O, Azuma T, Obata Y - J. Exp. Med. (1997)

Surface antigen profiles of spleen cells and thymocytes of  SCID mice transplanted with ED13.5 fetal liver cells. Cells were examined by two-color staining using various combinations of antibodies. The  expression of H-2Kb by spleen cells confirms their fetal liver origin. As for  T cell markers, Thy-1, TCRαβ, CD3, CD4, and CD8 were examined  and as for B cell makers, IgM and B220 were examined. Even relA−/−  fetal liver cells develop normally to mature T and B cells in the transplanted SCID mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196168&req=5

Figure 5: Surface antigen profiles of spleen cells and thymocytes of SCID mice transplanted with ED13.5 fetal liver cells. Cells were examined by two-color staining using various combinations of antibodies. The expression of H-2Kb by spleen cells confirms their fetal liver origin. As for T cell markers, Thy-1, TCRαβ, CD3, CD4, and CD8 were examined and as for B cell makers, IgM and B220 were examined. Even relA−/− fetal liver cells develop normally to mature T and B cells in the transplanted SCID mice.
Mentions: To test whether RelA-deficient stem cells can differentiate into T and B cells, the cell surface markers on lymphocytes of transplanted mice were examined. As shown in Fig. 5, the relA−/− hematopoietic stem cells differentiated to Thy1+/TCRαβ+ /CD3+/CD4+ or CD8+ T cells and IgM+/ B220+ B cells in the periphery, similarly to the relA+/+ and +/− stem cells. In addition, testing of the expression of activation markers of T cells, IL-2Rα (CD25) and CD44 (Pgp-1), revealed 6.6 and 2.5% of relA−/− spleen cells to be positive, respectively, with no significant differences from the relA+/+ or +/− cases (data not shown). The results with cells in lymph nodes were essentially identical to those of spleens (data not shown). The relA−/− thymuses with much fewer cells than those of relA+/+ and +/−, showed reduction of the CD4+/CD8+ immature population, which may have been caused by the absence of RelA. Altogether, these results suggested that RelA is not necessary for the maturation of lymphocytes or that the loss of RelA function can be compensated for by other members of the NF-κB family. In this regard, it was interesting to note that none of the mice deficient in any NF-κB subunit, whether RelA, c-Rel, RelB, or p50, showed abnormality in the development of T cells and B cells. There is a vast amount of evidence indicating the importance of NF-κB in lymphocyte development (for review see references 1, 3, 37). Thus, it is most likely that the development of T and B cells proceeds with certain combinations of NF-κB subunits and may not require the presence of specific NF-κB dimers.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.

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.

Show MeSH
Related in: MedlinePlus