RapamycinFungusV1, Main, Exploration, bibRecord, 000171

mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes.

Identifieur interne : 000171 ( Main/Exploration ); précédent : 000170; suivant : 000172

mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes.

Auteurs : Ariel L. Raybuck [États-Unis] ; Keunwook Lee [Corée du Sud] ; Sung Hoon Cho [États-Unis] ; Jingxin Li [États-Unis] ; James W. Thomas [États-Unis] ; Mark R. Boothby [États-Unis]

Source :

FASEB journal : official publication of the Federation of American Societies for Experimental Biology [ 1530-6860 ] ; 2019.

RBID : pubmed:31533002

Descripteurs français

English descriptors

KwdEn :
- Animals (MeSH), B-Lymphocytes (metabolism), Enzyme-Linked Immunosorbent Assay (MeSH), Flow Cytometry (MeSH), Immunoblotting (MeSH), Mechanistic Target of Rapamycin Complex 1 (genetics), Mechanistic Target of Rapamycin Complex 1 (metabolism), Mice (MeSH), Regulatory-Associated Protein of mTOR (genetics), Regulatory-Associated Protein of mTOR (metabolism), Signal Transduction (genetics), Signal Transduction (physiology).
MESH :
- chemical , genetics : Mechanistic Target of Rapamycin Complex 1, Regulatory-Associated Protein of mTOR.
- genetics : Signal Transduction.
- metabolism : B-Lymphocytes, Mechanistic Target of Rapamycin Complex 1, Regulatory-Associated Protein of mTOR.
- physiology : Signal Transduction.
- Animals, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunoblotting, Mice.

Abstract

Ample evidence indicates that nutrient concentrations in extracellular milieux affect signaling mediated by environmental sensor proteins. For instance, the mechanistic target of rapamycin (mTOR) is reduced during protein malnutrition and is known to be modulated by concentrations of several amino acids when in a multiprotein signaling complex that contains regulatory-associated protein of mTOR. We hypothesized that a partial decrease in mTOR complex 1 (mTORC1) activity intrinsic to B-lineage cells would perturb lymphocyte development or function, or both. We show that a cell-intrinsic decrease in mTORC1 activity impacted developmental progression, antigen receptor repertoire, and function along the B lineage. Thus, preimmune repertoires of B-lineage cells were altered in the marrow and periphery in a genetic model of regulatory-associated protein of mTOR haplo-insufficiency. An additional role for mTORC1 was revealed when a B-cell antigen receptor transgene was found to circumvent the abnormal B-cell development: haploinsufficient B cells were profoundly impaired in responses to antigen in vivo. Collectively, our findings indicate that mTORC1 serves as a rheostat that shapes differentiation along the B lineage, the preimmune repertoire, and antigen-driven selection of mature B cells. The findings also reveal a range in the impact of this nutrient sensor on activity-response relationships for distinct endpoints.-Raybuck, A. L., Lee, K., Cho, S. H., Li, J., Thomas, J. W., Boothby, M. R. mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes.

DOI: 10.1096/fj.201900069R
PubMed: 31533002
PubMed Central: PMC6894075

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000194
to stream Main, to step Curation: 000194

Le document en format XML

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<term>B-Lymphocytes (metabolism)</term>
<term>Enzyme-Linked Immunosorbent Assay (MeSH)</term>
<term>Flow Cytometry (MeSH)</term>
<term>Immunoblotting (MeSH)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (genetics)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (metabolism)</term>
<term>Mice (MeSH)</term>
<term>Regulatory-Associated Protein of mTOR (genetics)</term>
<term>Regulatory-Associated Protein of mTOR (metabolism)</term>
<term>Signal Transduction (genetics)</term>
<term>Signal Transduction (physiology)</term>
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<term>Complexe-1 cible mécanistique de la rapamycine (génétique)</term>
<term>Complexe-1 cible mécanistique de la rapamycine (métabolisme)</term>
<term>Cytométrie en flux (MeSH)</term>
<term>Immunotransfert (MeSH)</term>
<term>Lymphocytes B (métabolisme)</term>
<term>Protéine de régulation associée à mTOR (génétique)</term>
<term>Protéine de régulation associée à mTOR (métabolisme)</term>
<term>Souris (MeSH)</term>
<term>Test ELISA (MeSH)</term>
<term>Transduction du signal (génétique)</term>
<term>Transduction du signal (physiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Mechanistic Target of Rapamycin Complex 1</term>
<term>Regulatory-Associated Protein of mTOR</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Complexe-1 cible mécanistique de la rapamycine</term>
<term>Protéine de régulation associée à mTOR</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>B-Lymphocytes</term>
<term>Mechanistic Target of Rapamycin Complex 1</term>
<term>Regulatory-Associated Protein of mTOR</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Complexe-1 cible mécanistique de la rapamycine</term>
<term>Lymphocytes B</term>
<term>Protéine de régulation associée à mTOR</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Signal Transduction</term>
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<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Flow Cytometry</term>
<term>Immunoblotting</term>
<term>Mice</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cytométrie en flux</term>
<term>Immunotransfert</term>
<term>Souris</term>
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<front><div type="abstract" xml:lang="en">Ample evidence indicates that nutrient concentrations in extracellular milieux affect signaling mediated by environmental sensor proteins. For instance, the mechanistic target of rapamycin (mTOR) is reduced during protein malnutrition and is known to be modulated by concentrations of several amino acids when in a multiprotein signaling complex that contains regulatory-associated protein of mTOR. We hypothesized that a partial decrease in mTOR complex 1 (mTORC1) activity intrinsic to B-lineage cells would perturb lymphocyte development or function, or both. We show that a cell-intrinsic decrease in mTORC1 activity impacted developmental progression, antigen receptor repertoire, and function along the B lineage. Thus, preimmune repertoires of B-lineage cells were altered in the marrow and periphery in a genetic model of regulatory-associated protein of mTOR haplo-insufficiency. An additional role for mTORC1 was revealed when a B-cell antigen receptor transgene was found to circumvent the abnormal B-cell development: haploinsufficient B cells were profoundly impaired in responses to antigen <i>in vivo</i>
. Collectively, our findings indicate that mTORC1 serves as a rheostat that shapes differentiation along the B lineage, the preimmune repertoire, and antigen-driven selection of mature B cells. The findings also reveal a range in the impact of this nutrient sensor on activity-response relationships for distinct endpoints.-Raybuck, A. L., Lee, K., Cho, S. H., Li, J., Thomas, J. W., Boothby, M. R. mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes.</div>
</front>
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<ArticleTitle>mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes.</ArticleTitle>
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<Abstract><AbstractText>Ample evidence indicates that nutrient concentrations in extracellular milieux affect signaling mediated by environmental sensor proteins. For instance, the mechanistic target of rapamycin (mTOR) is reduced during protein malnutrition and is known to be modulated by concentrations of several amino acids when in a multiprotein signaling complex that contains regulatory-associated protein of mTOR. We hypothesized that a partial decrease in mTOR complex 1 (mTORC1) activity intrinsic to B-lineage cells would perturb lymphocyte development or function, or both. We show that a cell-intrinsic decrease in mTORC1 activity impacted developmental progression, antigen receptor repertoire, and function along the B lineage. Thus, preimmune repertoires of B-lineage cells were altered in the marrow and periphery in a genetic model of regulatory-associated protein of mTOR haplo-insufficiency. An additional role for mTORC1 was revealed when a B-cell antigen receptor transgene was found to circumvent the abnormal B-cell development: haploinsufficient B cells were profoundly impaired in responses to antigen <i>in vivo</i>
. Collectively, our findings indicate that mTORC1 serves as a rheostat that shapes differentiation along the B lineage, the preimmune repertoire, and antigen-driven selection of mature B cells. The findings also reveal a range in the impact of this nutrient sensor on activity-response relationships for distinct endpoints.-Raybuck, A. L., Lee, K., Cho, S. H., Li, J., Thomas, J. W., Boothby, M. R. mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes.</AbstractText>
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<ForeName>Keunwook</ForeName>
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<AffiliationInfo><Affiliation>Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
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<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
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<ArticleDate DateType="Electronic"><Year>2019</Year>
<Month>09</Month>
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	Serveur d'exploration sur la rapamycine et les champignons
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mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes.

mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes.

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