Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim sustains B lymphopoiesis in the absence of IL-7
Identifieur interne : 000589 ( Ncbi/Checkpoint ); précédent : 000588; suivant : 000590Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim sustains B lymphopoiesis in the absence of IL-7
Auteurs : Nicholas D. Huntington [France] ; Verena Labi [Autriche] ; Ana Cumano [France] ; Paulo Vieira [France] ; Andreas Strasser [Australie] ; Andreas Villunger [Autriche] ; James P. Di Santo [France] ; Nuno L. Alves [France]Source :
- International Immunology [ 0953-8178 ] ; 2009.
Abstract
IL-7 is pivotal for B cell development. Proteins of the Bcl-2 family are essential regulators of lymphocyte survival. Particularly, the pro-apoptotic BH3-only members Bim and Puma mediate lymphocyte apoptosis provoked by cytokine deprivation. Herein, we addressed whether the absence of Bim or Puma within the hematopoietic compartment could bypass the requirement for IL-7-driven B cell development in adult mice. We found that deficiency of Bim, but not Puma, partially rescued B cell development in the absence of IL-7. The numbers of both sIgM− and sIgM+ B cells were markedly increased in the bone marrow of recipients lacking IL-7 upon reconstitution with Bim-deficient hematopoietic progenitors, compared with their control or Puma-deficient counterparts. The augmentation of B cell lymphopoiesis in the absence of Bim was reflected in the mature peripheral compartment by an increase in both the number of immature and mature B cells in the spleen and in the circulating IgM levels. Bim-deficient B cells were also increased in IL-7-sufficient recipients suggesting that peripheral B cells homeostasis is governed by a Bim-dependent and IL-7-independent mechanism. Our data highlight the role of Bim as a key regulator of cell survival during B lymphocyte development
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DOI: 10.1093/intimm/dxp043
PubMed: 19454543
PubMed Central: 2980998
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Huntington</name><affiliation wicri:level="3"><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Cytokines and Lymphoid Development Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Inserm U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Labi, Verena" sort="Labi, Verena" uniqKey="Labi V" first="Verena" last="Labi">Verena Labi</name><affiliation wicri:level="1"><nlm:aff id="aff3">Division of Developmental Immunology, Department of Biocenter, Innsbruck Medical University, Innsbruck, Austria</nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Division of Developmental Immunology, Department of Biocenter, Innsbruck Medical University, Innsbruck</wicri:regionArea><wicri:noRegion>Innsbruck</wicri:noRegion></affiliation></author><author><name sortKey="Cumano, Ana" sort="Cumano, Ana" uniqKey="Cumano A" first="Ana" last="Cumano">Ana Cumano</name><affiliation wicri:level="3"><nlm:aff id="aff2">Inserm U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff4">Lymphocyte Development Unit, Institut Pasteur, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lymphocyte Development Unit, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Vieira, Paulo" sort="Vieira, Paulo" uniqKey="Vieira P" first="Paulo" last="Vieira">Paulo Vieira</name><affiliation wicri:level="3"><nlm:aff id="aff2">Inserm U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff4">Lymphocyte Development Unit, Institut Pasteur, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lymphocyte Development Unit, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Strasser, Andreas" sort="Strasser, Andreas" uniqKey="Strasser A" first="Andreas" last="Strasser">Andreas Strasser</name><affiliation wicri:level="1"><nlm:aff id="aff5">Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050</wicri:regionArea><wicri:noRegion>Victoria 3050</wicri:noRegion></affiliation></author><author><name sortKey="Villunger, Andreas" sort="Villunger, Andreas" uniqKey="Villunger A" first="Andreas" last="Villunger">Andreas Villunger</name><affiliation wicri:level="1"><nlm:aff id="aff3">Division of Developmental Immunology, Department of Biocenter, Innsbruck Medical University, Innsbruck, Austria</nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Division of Developmental Immunology, Department of Biocenter, Innsbruck Medical University, Innsbruck</wicri:regionArea><wicri:noRegion>Innsbruck</wicri:noRegion></affiliation></author><author><name sortKey="Di Santo, James P" sort="Di Santo, James P" uniqKey="Di Santo J" first="James P." last="Di Santo">James P. Di Santo</name><affiliation wicri:level="1"><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Cytokines and Lymphoid Development Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris</wicri:regionArea><wicri:noRegion>75724 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Inserm U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Alves, Nuno L" sort="Alves, Nuno L" uniqKey="Alves N" first="Nuno L." last="Alves">Nuno L. Alves</name><affiliation wicri:level="1"><nlm:aff id="aff1">Cytokines and Lymphoid Development Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Cytokines and Lymphoid Development Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris</wicri:regionArea><wicri:noRegion>75724 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Inserm U668, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm U668, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">International Immunology</title><idno type="ISSN">0953-8178</idno><idno type="eISSN">1460-2377</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>IL-7 is pivotal for B cell development. Proteins of the Bcl-2 family are essential regulators of lymphocyte survival. Particularly, the pro-apoptotic BH3-only members Bim and Puma mediate lymphocyte apoptosis provoked by cytokine deprivation. Herein, we addressed whether the absence of Bim or Puma within the hematopoietic compartment could bypass the requirement for IL-7-driven B cell development in adult mice. We found that deficiency of Bim, but not Puma, partially rescued B cell development in the absence of IL-7. The numbers of both sIgM<sup>−</sup> and sIgM<sup>+</sup> B cells were markedly increased in the bone marrow of recipients lacking IL-7 upon reconstitution with Bim-deficient hematopoietic progenitors, compared with their control or Puma-deficient counterparts. The augmentation of B cell lymphopoiesis in the absence of Bim was reflected in the mature peripheral compartment by an increase in both the number of immature and mature B cells in the spleen and in the circulating IgM levels. Bim-deficient B cells were also increased in IL-7-sufficient recipients suggesting that peripheral B cells homeostasis is governed by a Bim-dependent and IL-7-independent mechanism. Our data highlight the role of Bim as a key regulator of cell survival during B lymphocyte development <italic>in vivo</italic>.</p></div></front></TEI><affiliations><list><country><li>Australie</li><li>Autriche</li><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D." last="Huntington">Nicholas D. Huntington</name></region><name sortKey="Alves, Nuno L" sort="Alves, Nuno L" uniqKey="Alves N" first="Nuno L." last="Alves">Nuno L. Alves</name><name sortKey="Alves, Nuno L" sort="Alves, Nuno L" uniqKey="Alves N" first="Nuno L." last="Alves">Nuno L. Alves</name><name sortKey="Cumano, Ana" sort="Cumano, Ana" uniqKey="Cumano A" first="Ana" last="Cumano">Ana Cumano</name><name sortKey="Cumano, Ana" sort="Cumano, Ana" uniqKey="Cumano A" first="Ana" last="Cumano">Ana Cumano</name><name sortKey="Di Santo, James P" sort="Di Santo, James P" uniqKey="Di Santo J" first="James P." last="Di Santo">James P. Di Santo</name><name sortKey="Di Santo, James P" sort="Di Santo, James P" uniqKey="Di Santo J" first="James P." last="Di Santo">James P. Di Santo</name><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D." last="Huntington">Nicholas D. Huntington</name><name sortKey="Vieira, Paulo" sort="Vieira, Paulo" uniqKey="Vieira P" first="Paulo" last="Vieira">Paulo Vieira</name><name sortKey="Vieira, Paulo" sort="Vieira, Paulo" uniqKey="Vieira P" first="Paulo" last="Vieira">Paulo Vieira</name></country><country name="Autriche"><noRegion><name sortKey="Labi, Verena" sort="Labi, Verena" uniqKey="Labi V" first="Verena" last="Labi">Verena Labi</name></noRegion><name sortKey="Villunger, Andreas" sort="Villunger, Andreas" uniqKey="Villunger A" first="Andreas" last="Villunger">Andreas Villunger</name></country><country name="Australie"><noRegion><name sortKey="Strasser, Andreas" sort="Strasser, Andreas" uniqKey="Strasser A" first="Andreas" last="Strasser">Andreas Strasser</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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