Diacylglycerol kinase ¿ promotes actin cytoskeleton remodeling and mechanical forces at the B cell immune synapse

Autor: Sara V. Merino-Cortes, Paolo Pierobon, Ana-Maria Lennon Dumenil, Yolanda R. Carrasco, Ana Martínez-Riaño, Sara Roman-Garcia, Rosa Liébana, Julien Husson, Sofia R. Gardeta, Balbino Alarcón, Judith Pineau, Isabel Mérida
Přispěvatelé: Ministerio de Economía y Competitividad (España), Worldwide Cancer Research, LabexMER, Agence Nationale de la Recherche (France), Centre National de la Recherche Scientifique (France), Centro Nacional de Biotecnología [Madrid] (CNB-CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'hydrodynamique (LadHyX), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Pierobon, Paolo
Rok vydání: 2020
Předmět:
Diacylglycerol Kinase
Immunological Synapses
T cell
Lymphocyte
[SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biochemistry
Immunological synapse
Mice
03 medical and health sciences
0302 clinical medicine
Antigen
medicine
Animals
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
Molecular Biology
Cytoskeleton
B cell
030304 developmental biology
Diacylglycerol kinase
Mice
Knockout
B-Lymphocytes
0303 health sciences
Chemistry
Germinal center
Actin remodeling
Cell Biology
3. Good health
Cell biology
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
medicine.anatomical_structure
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology
[SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology
030217 neurology & neurosurgery
Zdroj: Science Signaling
Science Signaling, American Association for the Advancement of Science, 2020, 13 (627), pp.eaaw8214. ⟨10.1126/scisignal.aaw8214⟩
Science Signaling, 2020, 13 (627), pp.eaaw8214. ⟨10.1126/scisignal.aaw8214⟩
Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 1937-9145
DOI: 10.1126/scisignal.aaw8214⟩
Popis: Diacylglycerol kinases (DGKs) limit antigen receptor signaling in immune cells by consuming the second messenger diacylglycerol (DAG) to generate phosphatidic acid (PA). Here, we showed that DGKζ promotes lymphocyte function–associated antigen 1 (LFA-1)–mediated adhesion and F-actin generation at the immune synapse of B cells with antigen-presenting cells (APCs), mostly in a PA-dependent manner. Measurement of single-cell mechanical force generation indicated that DGKζ-deficient B cells exerted lower forces at the immune synapse than did wild-type B cells. Nonmuscle myosin activation and translocation of the microtubule-organizing center (MTOC) to the immune synapse were also impaired in DGKζ-deficient B cells. These functional defects correlated with the decreased ability of B cells to present antigen and activate T cells in vitro. The in vivo germinal center response of DGKζ-deficient B cells was also reduced compared with that of wild-type B cells, indicating that loss of DGKζ in B cells impaired T cell help. Together, our data suggest that DGKζ shapes B cell responses by regulating actin remodeling, force generation, and antigen uptake–related events at the immune synapse. Hence, an appropriate balance in the amounts of DAG and PA is required for optimal B cell function.
SVMC is supported by an FPI contract from the Spanish Ministry of Economy (MINECO; BES-2014-068006). This work was supported by grants from the MINECO (BFU2013-48828-P) and from the Worldwide Cancer Research (WCR; grant reference number 15-1322). JH has benefited from the financial support of the LabeX LaSIPS (ANR-10-LABX-0040-LaSIPS) managed by the French National Research Agency under the “Investissements d’avenir” program (nº ANR-11-IDEX-0003-02), and from a PEPS CNRS funding.
Databáze: OpenAIRE
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