TocilizumabV1, Main, Exploration, bibRecord, 002068

Cutting edge: circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production.

Identifieur interne : 002068 ( Main/Exploration ); précédent : 002067; suivant : 002069

Cutting edge: circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production.

Auteurs : Konstantia-Maria Chavele [Royaume-Uni] ; Eve Merry [Royaume-Uni] ; Michael R. Ehrenstein [Royaume-Uni]

Source :

Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2015.

RBID : pubmed:25681343

Descripteurs français

English descriptors

KwdEn :
- Antibodies, Monoclonal, Humanized (immunology), Antibodies, Monoclonal, Humanized (therapeutic use), Antigens, CD19 (immunology), Antigens, CD19 (metabolism), Arthritis, Rheumatoid (blood), Arthritis, Rheumatoid (drug therapy), Arthritis, Rheumatoid (immunology), B-Lymphocytes (immunology), B-Lymphocytes (metabolism), CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (metabolism), Cell Differentiation (immunology), Cell Proliferation, Cells, Cultured, Coculture Techniques, DNA-Binding Proteins (immunology), DNA-Binding Proteins (metabolism), Flow Cytometry, Humans, Inducible T-Cell Co-Stimulator Protein (immunology), Inducible T-Cell Co-Stimulator Protein (metabolism), Interleukin-6 (immunology), Interleukin-6 (metabolism), Interleukins (immunology), Interleukins (metabolism), Plasma Cells (immunology), Plasma Cells (metabolism), Proto-Oncogene Proteins c-bcl-6, Receptors, CXCR5 (immunology), Receptors, CXCR5 (metabolism), T-Lymphocytes, Helper-Inducer (immunology), T-Lymphocytes, Helper-Inducer (metabolism).
MESH :
- chemical , immunology : Antibodies, Monoclonal, Humanized, Antigens, CD19, DNA-Binding Proteins, Inducible T-Cell Co-Stimulator Protein, Interleukin-6, Interleukins, Receptors, CXCR5.
- chemical , metabolism : Antigens, CD19, DNA-Binding Proteins, Inducible T-Cell Co-Stimulator Protein, Interleukin-6, Interleukins, Receptors, CXCR5.
- chemical , therapeutic use : Antibodies, Monoclonal, Humanized.
- blood : Arthritis, Rheumatoid.
- drug therapy : Arthritis, Rheumatoid.
- immunology : Arthritis, Rheumatoid, B-Lymphocytes, CD4-Positive T-Lymphocytes, Cell Differentiation, Plasma Cells, T-Lymphocytes, Helper-Inducer.
- metabolism : B-Lymphocytes, CD4-Positive T-Lymphocytes, Plasma Cells, T-Lymphocytes, Helper-Inducer.
- Cell Proliferation, Cells, Cultured, Coculture Techniques, Flow Cytometry, Humans, Proto-Oncogene Proteins c-bcl-6.

Abstract

B cells require CD4(+) T follicular helper (Tfh) cells to progress through the germinal center and provide protective Ab responses. In this article, we reveal a reciprocal interaction whereby circulating human plasmablasts are potent inducers of the Tfh cell-differentiation program, including the expression of their key transcription factor Bcl-6. The markedly increased propensity of plasmablasts, compared with naive B cells, to induce Tfh cell differentiation was due to their increased production of IL-6. Specific targeting of IL-6 using tocilizumab therapy in patients with rheumatoid arthritis led to a significant reduction in circulating Tfh cell numbers and IL-21 production, which was correlated with reduced plasmablast formation. Our data uncover a positive-feedback loop between circulating plasmablasts and Tfh cells that could sustain autoimmunity and spread Ab-driven inflammation to unaffected sites; this represents an important therapeutic target, as well as reveals a novel mechanism of action for tocilizumab.

DOI: 10.4049/jimmunol.1401190
PubMed: 25681343

Affiliations:

Le document en format XML

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<term>Antigens, CD19 (immunology)</term>
<term>Antigens, CD19 (metabolism)</term>
<term>Arthritis, Rheumatoid (blood)</term>
<term>Arthritis, Rheumatoid (drug therapy)</term>
<term>Arthritis, Rheumatoid (immunology)</term>
<term>B-Lymphocytes (immunology)</term>
<term>B-Lymphocytes (metabolism)</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD4-Positive T-Lymphocytes (metabolism)</term>
<term>Cell Differentiation (immunology)</term>
<term>Cell Proliferation</term>
<term>Cells, Cultured</term>
<term>Coculture Techniques</term>
<term>DNA-Binding Proteins (immunology)</term>
<term>DNA-Binding Proteins (metabolism)</term>
<term>Flow Cytometry</term>
<term>Humans</term>
<term>Inducible T-Cell Co-Stimulator Protein (immunology)</term>
<term>Inducible T-Cell Co-Stimulator Protein (metabolism)</term>
<term>Interleukin-6 (immunology)</term>
<term>Interleukin-6 (metabolism)</term>
<term>Interleukins (immunology)</term>
<term>Interleukins (metabolism)</term>
<term>Plasma Cells (immunology)</term>
<term>Plasma Cells (metabolism)</term>
<term>Proto-Oncogene Proteins c-bcl-6</term>
<term>Receptors, CXCR5 (immunology)</term>
<term>Receptors, CXCR5 (metabolism)</term>
<term>T-Lymphocytes, Helper-Inducer (immunology)</term>
<term>T-Lymphocytes, Helper-Inducer (metabolism)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Anticorps monoclonaux humanisés (immunologie)</term>
<term>Anticorps monoclonaux humanisés (usage thérapeutique)</term>
<term>Antigènes CD19 (immunologie)</term>
<term>Antigènes CD19 (métabolisme)</term>
<term>Cellules cultivées</term>
<term>Cytométrie en flux</term>
<term>Différenciation cellulaire (immunologie)</term>
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<term>Lymphocytes B (immunologie)</term>
<term>Lymphocytes B (métabolisme)</term>
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<term>Lymphocytes T CD4+ (métabolisme)</term>
<term>Lymphocytes T auxiliaires (immunologie)</term>
<term>Lymphocytes T auxiliaires (métabolisme)</term>
<term>Plasmocytes (immunologie)</term>
<term>Plasmocytes (métabolisme)</term>
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<term>Polyarthrite rhumatoïde (sang)</term>
<term>Polyarthrite rhumatoïde (traitement médicamenteux)</term>
<term>Prolifération cellulaire</term>
<term>Protéine inductible de costimulation du lymphocyte T (immunologie)</term>
<term>Protéine inductible de costimulation du lymphocyte T (métabolisme)</term>
<term>Protéines de liaison à l'ADN (immunologie)</term>
<term>Protéines de liaison à l'ADN (métabolisme)</term>
<term>Protéines proto-oncogènes c-bcl-6</term>
<term>Récepteurs CXCR5 (immunologie)</term>
<term>Récepteurs CXCR5 (métabolisme)</term>
<term>Techniques de coculture</term>
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<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term>
<term>Antigens, CD19</term>
<term>DNA-Binding Proteins</term>
<term>Inducible T-Cell Co-Stimulator Protein</term>
<term>Interleukin-6</term>
<term>Interleukins</term>
<term>Receptors, CXCR5</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antigens, CD19</term>
<term>DNA-Binding Proteins</term>
<term>Inducible T-Cell Co-Stimulator Protein</term>
<term>Interleukin-6</term>
<term>Interleukins</term>
<term>Receptors, CXCR5</term>
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<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Arthritis, Rheumatoid</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Arthritis, Rheumatoid</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term>
<term>Antigènes CD19</term>
<term>Différenciation cellulaire</term>
<term>Interleukine-6</term>
<term>Interleukines</term>
<term>Lymphocytes B</term>
<term>Lymphocytes T CD4+</term>
<term>Lymphocytes T auxiliaires</term>
<term>Plasmocytes</term>
<term>Polyarthrite rhumatoïde</term>
<term>Protéine inductible de costimulation du lymphocyte T</term>
<term>Protéines de liaison à l'ADN</term>
<term>Récepteurs CXCR5</term>
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<term>B-Lymphocytes</term>
<term>CD4-Positive T-Lymphocytes</term>
<term>Cell Differentiation</term>
<term>Plasma Cells</term>
<term>T-Lymphocytes, Helper-Inducer</term>
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<term>CD4-Positive T-Lymphocytes</term>
<term>Plasma Cells</term>
<term>T-Lymphocytes, Helper-Inducer</term>
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<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes CD19</term>
<term>Interleukine-6</term>
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<term>Lymphocytes B</term>
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<term>Lymphocytes T auxiliaires</term>
<term>Plasmocytes</term>
<term>Protéine inductible de costimulation du lymphocyte T</term>
<term>Protéines de liaison à l'ADN</term>
<term>Récepteurs CXCR5</term>
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</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Cell Proliferation</term>
<term>Cells, Cultured</term>
<term>Coculture Techniques</term>
<term>Flow Cytometry</term>
<term>Humans</term>
<term>Proto-Oncogene Proteins c-bcl-6</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Cellules cultivées</term>
<term>Cytométrie en flux</term>
<term>Humains</term>
<term>Prolifération cellulaire</term>
<term>Protéines proto-oncogènes c-bcl-6</term>
<term>Techniques de coculture</term>
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<front><div type="abstract" xml:lang="en">B cells require CD4(+) T follicular helper (Tfh) cells to progress through the germinal center and provide protective Ab responses. In this article, we reveal a reciprocal interaction whereby circulating human plasmablasts are potent inducers of the Tfh cell-differentiation program, including the expression of their key transcription factor Bcl-6. The markedly increased propensity of plasmablasts, compared with naive B cells, to induce Tfh cell differentiation was due to their increased production of IL-6. Specific targeting of IL-6 using tocilizumab therapy in patients with rheumatoid arthritis led to a significant reduction in circulating Tfh cell numbers and IL-21 production, which was correlated with reduced plasmablast formation. Our data uncover a positive-feedback loop between circulating plasmablasts and Tfh cells that could sustain autoimmunity and spread Ab-driven inflammation to unaffected sites; this represents an important therapeutic target, as well as reveals a novel mechanism of action for tocilizumab. </div>
</front>
</TEI>
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<li>Grand Londres</li>
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<tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Chavele, Konstantia Maria" sort="Chavele, Konstantia Maria" uniqKey="Chavele K" first="Konstantia-Maria" last="Chavele">Konstantia-Maria Chavele</name>
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<name sortKey="Ehrenstein, Michael R" sort="Ehrenstein, Michael R" uniqKey="Ehrenstein M" first="Michael R" last="Ehrenstein">Michael R. Ehrenstein</name>
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Cutting edge: circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production.

Cutting edge: circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production.

Source :

Descripteurs français

English descriptors

Abstract

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

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

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