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Título: | Diacylglycerol kinase ¿ promotes actin cytoskeleton remodeling and mechanical forces at the B cell immune synapse |
Autor: | Merino-Cortés, Sara V.; Gardeta, Sofía; Román-García, Sara; Martínez-Riaño, Ana; Pineau, Judith; Liébana, Rosa CSIC ORCID; Mérida, Isabel CSIC ORCID ; Lennon Dumenil, Ana-María; Pierobon, Paolo; Husson, Julien; Alarcón, Balbino CSIC ORCID; Carrasco, Yolanda R. | Fecha de publicación: | 14-abr-2020 | Editor: | American Association for the Advancement of Science | Citación: | Science signaling 13(627): eaaw8214 (2020) | Resumen: | 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. | Versión del editor: | http://dx.doi.org/10.1126/scisignal.aaw8214 | URI: | http://hdl.handle.net/10261/228928 | DOI: | 10.1126/scisignal.aaw8214 | ISSN: | 1945-0877 | E-ISSN: | 1937-9145 |
Aparece en las colecciones: | (CBM) Artículos (CNB) Artículos |
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