Diacylglycerol kinase ζ promotes actin cytoskeleton remodeling and mechanical forces at the B cell immune synapse
- PMID: 32291315
- DOI: 10.1126/scisignal.aaw8214
Diacylglycerol kinase ζ promotes actin cytoskeleton remodeling and mechanical forces at the B cell immune synapse
Abstract
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.
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Similar articles
-
Interplay Between SNX27 and DAG Metabolism in the Control of Trafficking and Signaling at the IS.Int J Mol Sci. 2020 Jun 15;21(12):4254. doi: 10.3390/ijms21124254. Int J Mol Sci. 2020. PMID: 32549284 Free PMC article. Review.
-
Diacylglycerol kinase ζ limits the polarized recruitment of diacylglycerol-enriched organelles to the immune synapse in T cells.Sci Signal. 2016 Dec 20;9(459):ra127. doi: 10.1126/scisignal.aaf7714. Sci Signal. 2016. PMID: 27999176
-
Diacylglycerol kinase ζ controls diacylglycerol metabolism at the immunological synapse.Mol Biol Cell. 2011 Nov;22(22):4406-14. doi: 10.1091/mbc.E11-03-0247. Epub 2011 Sep 21. Mol Biol Cell. 2011. PMID: 21937721 Free PMC article.
-
Diacylglycerol kinase α establishes T cell polarity by shaping diacylglycerol accumulation at the immunological synapse.Sci Signal. 2014 Aug 26;7(340):ra82. doi: 10.1126/scisignal.2005287. Sci Signal. 2014. PMID: 25161317 Free PMC article.
-
Diacylglycerol Kinases: Shaping Diacylglycerol and Phosphatidic Acid Gradients to Control Cell Polarity.Front Cell Dev Biol. 2016 Nov 29;4:140. doi: 10.3389/fcell.2016.00140. eCollection 2016. Front Cell Dev Biol. 2016. PMID: 27965956 Free PMC article. Review.
Cited by
-
A B-cell actomyosin arc network couples integrin co-stimulation to mechanical force-dependent immune synapse formation.Elife. 2022 Apr 11;11:e72805. doi: 10.7554/eLife.72805. Elife. 2022. PMID: 35404237 Free PMC article.
-
Rapid viscoelastic changes are a hallmark of early leukocyte activation.Biophys J. 2021 May 4;120(9):1692-1704. doi: 10.1016/j.bpj.2021.02.042. Epub 2021 Mar 17. Biophys J. 2021. PMID: 33730552 Free PMC article.
-
A spatiotemporal map of co-receptor signaling networks underlying B cell activation.Cell Rep. 2024 Jun 25;43(6):114332. doi: 10.1016/j.celrep.2024.114332. Epub 2024 Jun 7. Cell Rep. 2024. PMID: 38850533 Free PMC article.
-
Interplay Between SNX27 and DAG Metabolism in the Control of Trafficking and Signaling at the IS.Int J Mol Sci. 2020 Jun 15;21(12):4254. doi: 10.3390/ijms21124254. Int J Mol Sci. 2020. PMID: 32549284 Free PMC article. Review.
-
Sorting Nexin 27 Enables MTOC and Secretory Machinery Translocation to the Immune Synapse.Front Immunol. 2022 Jan 12;12:814570. doi: 10.3389/fimmu.2021.814570. eCollection 2021. Front Immunol. 2022. PMID: 35095913 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous