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Beta-catenin is dispensable for hematopoiesis and lymphopoiesis.

Cobas M, Wilson A, Ernst B, Mancini SJ, MacDonald HR, Kemler R, Radtke F - J. Exp. Med. (2004)

Bottom Line: Beta-catenin-mediated Wnt signaling has been suggested to be critically involved in hematopoietic stem cell maintenance and development of T and B cells in the immune system.Unexpectedly, here we report that inducible Cre-loxP-mediated inactivation of the beta-catenin gene in bone marrow progenitors does not impair their ability to self-renew and reconstitute all hematopoietic lineages (myeloid, erythroid, and lymphoid), even in competitive mixed chimeras.In addition, both thymocyte survival and antigen-induced proliferation of peripheral T cells is beta-catenin independent.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.

ABSTRACT
Beta-catenin-mediated Wnt signaling has been suggested to be critically involved in hematopoietic stem cell maintenance and development of T and B cells in the immune system. Unexpectedly, here we report that inducible Cre-loxP-mediated inactivation of the beta-catenin gene in bone marrow progenitors does not impair their ability to self-renew and reconstitute all hematopoietic lineages (myeloid, erythroid, and lymphoid), even in competitive mixed chimeras. In addition, both thymocyte survival and antigen-induced proliferation of peripheral T cells is beta-catenin independent. In contrast to earlier reports, these data exclude an essential role for beta-catenin during hematopoiesis and lymphopoiesis.

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Related in: MedlinePlus

Loss of β-catenin does not perturb antigen-induced T cell proliferation. CFSE-labeled splenocytes isolated from mixed BM chimeras were transferred i.v. into WT mice. The next day mice were injected i.p. with 20 μg SEB. 2 d later the draining popliteal LNs were removed and analyzed by FACS®. After gating on CD45.1+ (WT donor) or CD45.2+ (β-catenin−/− donor), the number of cell divisions in Vβ8− (negative control), CD8+ Vβ8+, and CD4+ Vβ8+ populations are shown. One representative experiment out of four is shown.
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fig6: Loss of β-catenin does not perturb antigen-induced T cell proliferation. CFSE-labeled splenocytes isolated from mixed BM chimeras were transferred i.v. into WT mice. The next day mice were injected i.p. with 20 μg SEB. 2 d later the draining popliteal LNs were removed and analyzed by FACS®. After gating on CD45.1+ (WT donor) or CD45.2+ (β-catenin−/− donor), the number of cell divisions in Vβ8− (negative control), CD8+ Vβ8+, and CD4+ Vβ8+ populations are shown. One representative experiment out of four is shown.

Mentions: Because β-catenin–mediated Wnt signaling influences proliferation of many different cell types, we wanted to test whether the absence of β-catenin in peripheral T cells influences their ability to proliferate in response to antigen. For this purpose peripheral T cells were isolated from either control or β-catenin−/− mixed BM chimeras, labeled with the fluorescent dye CSFE, and then transferred into recipient mice. 24 h after transfer of the labeled cells the mice were injected with SEB and proliferation of the antigen-specific T cells was monitored 2 d after antigen challenge. Transferring a mixed population of CD45.1+ WT and CD45.2+ β-catenin−/− T cells derived from mixed BM chimeras permits a direct comparison of antigen-induced proliferation of CD8+ and CD4+ T cells within the same mouse. As shown in Fig. 6 , antigen-specific proliferation of CD8+ Vβ8+ and CD4+ Vβ8+ cells was indistinguishable between CD45.1+ WT and CD45.2+ β-catenin–deficient populations. The results indicate that β-catenin is also dispensable for antigen-induced T cell proliferation.


Beta-catenin is dispensable for hematopoiesis and lymphopoiesis.

Cobas M, Wilson A, Ernst B, Mancini SJ, MacDonald HR, Kemler R, Radtke F - J. Exp. Med. (2004)

Loss of β-catenin does not perturb antigen-induced T cell proliferation. CFSE-labeled splenocytes isolated from mixed BM chimeras were transferred i.v. into WT mice. The next day mice were injected i.p. with 20 μg SEB. 2 d later the draining popliteal LNs were removed and analyzed by FACS®. After gating on CD45.1+ (WT donor) or CD45.2+ (β-catenin−/− donor), the number of cell divisions in Vβ8− (negative control), CD8+ Vβ8+, and CD4+ Vβ8+ populations are shown. One representative experiment out of four is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211763&req=5

fig6: Loss of β-catenin does not perturb antigen-induced T cell proliferation. CFSE-labeled splenocytes isolated from mixed BM chimeras were transferred i.v. into WT mice. The next day mice were injected i.p. with 20 μg SEB. 2 d later the draining popliteal LNs were removed and analyzed by FACS®. After gating on CD45.1+ (WT donor) or CD45.2+ (β-catenin−/− donor), the number of cell divisions in Vβ8− (negative control), CD8+ Vβ8+, and CD4+ Vβ8+ populations are shown. One representative experiment out of four is shown.
Mentions: Because β-catenin–mediated Wnt signaling influences proliferation of many different cell types, we wanted to test whether the absence of β-catenin in peripheral T cells influences their ability to proliferate in response to antigen. For this purpose peripheral T cells were isolated from either control or β-catenin−/− mixed BM chimeras, labeled with the fluorescent dye CSFE, and then transferred into recipient mice. 24 h after transfer of the labeled cells the mice were injected with SEB and proliferation of the antigen-specific T cells was monitored 2 d after antigen challenge. Transferring a mixed population of CD45.1+ WT and CD45.2+ β-catenin−/− T cells derived from mixed BM chimeras permits a direct comparison of antigen-induced proliferation of CD8+ and CD4+ T cells within the same mouse. As shown in Fig. 6 , antigen-specific proliferation of CD8+ Vβ8+ and CD4+ Vβ8+ cells was indistinguishable between CD45.1+ WT and CD45.2+ β-catenin–deficient populations. The results indicate that β-catenin is also dispensable for antigen-induced T cell proliferation.

Bottom Line: Beta-catenin-mediated Wnt signaling has been suggested to be critically involved in hematopoietic stem cell maintenance and development of T and B cells in the immune system.Unexpectedly, here we report that inducible Cre-loxP-mediated inactivation of the beta-catenin gene in bone marrow progenitors does not impair their ability to self-renew and reconstitute all hematopoietic lineages (myeloid, erythroid, and lymphoid), even in competitive mixed chimeras.In addition, both thymocyte survival and antigen-induced proliferation of peripheral T cells is beta-catenin independent.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.

ABSTRACT
Beta-catenin-mediated Wnt signaling has been suggested to be critically involved in hematopoietic stem cell maintenance and development of T and B cells in the immune system. Unexpectedly, here we report that inducible Cre-loxP-mediated inactivation of the beta-catenin gene in bone marrow progenitors does not impair their ability to self-renew and reconstitute all hematopoietic lineages (myeloid, erythroid, and lymphoid), even in competitive mixed chimeras. In addition, both thymocyte survival and antigen-induced proliferation of peripheral T cells is beta-catenin independent. In contrast to earlier reports, these data exclude an essential role for beta-catenin during hematopoiesis and lymphopoiesis.

Show MeSH
Related in: MedlinePlus