{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:25Z","timestamp":1792790365682,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,27]]},"group-title":"Immunology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R35GM146935"],"award-info":[{"award-number":["R35GM146935"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T34GM136466"],"award-info":[{"award-number":["T34GM136466"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Damon Runyon Cancer Research Foundation","award":["DRR-85-25"],"award-info":[{"award-number":["DRR-85-25"]}],"id":[{"id":"https:\/\/ror.org\/01gd7b947","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. National Science Foundation","award":["2240176"],"award-info":[{"award-number":["2240176"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. National Science Foundation","award":["CNS-1725797"],"award-info":[{"award-number":["CNS-1725797"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. National Science Foundation","award":["DMR 2308708"],"award-info":[{"award-number":["DMR 2308708"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"crossref"}]},{"name":"United States Army Research Office","award":["W911NF2320006"],"award-info":[{"award-number":["W911NF2320006"]}],"id":[{"id":"https:\/\/ror.org\/05epdh915","id-type":"ROR","asserted-by":"crossref"}]},{"award":["R21CA301306"],"award-info":[{"award-number":["R21CA301306"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/01bj3aw27","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Antibodies engage both activating Fc Receptors and the inhibitory receptor Fc\u03b3RIIB. Why macrophages need a dedicated inhibitory receptor rather than simply tuning activating receptor signaling is unclear. Using DNA-based chimeric receptors and in silico modeling, we independently controlled activating and inhibitory Fc Receptors. We found that Fc\u03b3RIIB imposed a time limit on macrophage phagocytosis and ERK signaling. The time limit is due to activating Fc Receptors converting PI(4,5)P2 to PI(3,4,5)P3, which is subsequently converted to PI(3,4)P2 by Fc\u03b3RIIB. This leads to a pulse of active signaling, which is sufficient for phagocytosis of small bacteria-sized targets but not phagocytosis of large targets and TNF\u03b1 secretion. Unlike engaging Fc\u03b3RIIB, reducing activating Fc Receptor signaling decreased initiation of phagocytosis, the speed of PI(3,4,5)P3 generation, and the amplitude of ERK signaling. Our results demonstrate that Fc\u03b3RIIB controls the duration of IgG signaling, while the activating Fc Receptors control sensitivity.<\/jats:p>","DOI":"10.64898\/2026.09.21.753242","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:55:15Z","timestamp":1790571315000},"source":"Crossref","is-referenced-by-count":0,"title":["Inhibitory Fc Receptor sets a time limit on macrophage response to IgG"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5300-8151","authenticated-orcid":false,"given":"Annalise","family":"Bond","sequence":"first","affiliation":[{"name":"Molecular Cellular and Developmental Biology Department, University of California; Santa Barbara, Santa Barbara, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8850-0687","authenticated-orcid":false,"given":"Erika T","family":"Snyder","sequence":"additional","affiliation":[{"name":"Molecular Cellular and Developmental Biology Department, University of California; Santa Barbara, Santa Barbara, CA, USA"},{"name":"Interdisciplinary Quantitative Biosciences Program, University of California; Santa Barbara, Santa Barbara, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5031-2888","authenticated-orcid":false,"given":"Andrew","family":"Manion","sequence":"additional","affiliation":[{"name":"Molecular Cellular and Developmental Biology Department, University of California; Santa Barbara, Santa Barbara, CA, USA"},{"name":"Interdisciplinary Quantitative Biosciences Program, University of California; Santa Barbara, Santa Barbara, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9181-6012","authenticated-orcid":false,"given":"Catherine","family":"Hardy","sequence":"additional","affiliation":[{"name":"Molecular Cellular and Developmental Biology Department, University of California; Santa Barbara, Santa Barbara, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5751-231X","authenticated-orcid":false,"given":"Kenny","family":"Kieu","sequence":"additional","affiliation":[{"name":"Molecular Cellular and Developmental Biology Department, University of California; Santa Barbara, Santa Barbara, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0768-7004","authenticated-orcid":false,"given":"Maxwell Z","family":"Wilson","sequence":"additional","affiliation":[{"name":"Molecular Cellular and Developmental Biology Department, University of California; Santa Barbara, Santa Barbara, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7630-7429","authenticated-orcid":false,"given":"Enoch","family":"Yeung","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, University of California, Santa Barbara; Santa Barbara, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0531-4864","authenticated-orcid":false,"given":"Meghan A","family":"Morrissey","sequence":"additional","affiliation":[{"name":"Molecular Cellular and Developmental Biology Department, University of California; Santa Barbara, Santa Barbara, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100808351439000_2026.09.21.753242v3.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.026"},{"key":"2026100808351439000_2026.09.21.753242v3.2","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2015.1011450"},{"key":"2026100808351439000_2026.09.21.753242v3.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.10.007"},{"key":"2026100808351439000_2026.09.21.753242v3.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.08.004"},{"key":"2026100808351439000_2026.09.21.753242v3.5","doi-asserted-by":"publisher","DOI":"10.1038\/nri2206"},{"key":"2026100808351439000_2026.09.21.753242v3.6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117701"},{"key":"2026100808351439000_2026.09.21.753242v3.7","doi-asserted-by":"publisher","DOI":"10.1038\/nri2762"},{"key":"2026100808351439000_2026.09.21.753242v3.8","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.4049\/jimmunol.1302934","article-title":"Inhibitory Fc\u03b3 Receptor Is Required for the Maintenance of Tolerance through Distinct Mechanisms","volume":"192","year":"2014","journal-title":"The Journal of Immunology"},{"key":"2026100808351439000_2026.09.21.753242v3.9","doi-asserted-by":"crossref","first-page":"340","DOI":"10.4049\/jimmunol.1202250","article-title":"Fc\u03b3RIIb on Myeloid Cells and Intrinsic Renal Cells Rather than B Cells Protects from Nephrotoxic Nephritis","volume":"190","year":"2013","journal-title":"The Journal of Immunology"},{"key":"2026100808351439000_2026.09.21.753242v3.10","doi-asserted-by":"crossref","first-page":"5540","DOI":"10.4049\/jimmunol.1303272","article-title":"Fc\u03b3RIIb on Myeloid Cells Rather than on B Cells Protects from Collagen-Induced Arthritis","volume":"192","year":"2014","journal-title":"The Journal of Immunology"},{"key":"2026100808351439000_2026.09.21.753242v3.11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.1.179"},{"key":"2026100808351439000_2026.09.21.753242v3.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0352-z"},{"key":"2026100808351439000_2026.09.21.753242v3.13","doi-asserted-by":"crossref","unstructured":"A. Bond , M. A. Morrissey , Biochemical and biophysical mechanisms macrophages use to tune phagocytic appetite. Journal of Cell Science 138, JCS263513 (2025).","DOI":"10.1242\/jcs.263513"},{"key":"2026100808351439000_2026.09.21.753242v3.14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1118948"},{"key":"2026100808351439000_2026.09.21.753242v3.15","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0120"},{"key":"2026100808351439000_2026.09.21.753242v3.16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68311"},{"key":"2026100808351439000_2026.09.21.753242v3.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109057118"},{"key":"2026100808351439000_2026.09.21.753242v3.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.03.006"},{"key":"2026100808351439000_2026.09.21.753242v3.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80337-2"},{"key":"2026100808351439000_2026.09.21.753242v3.20","doi-asserted-by":"publisher","DOI":"10.1038\/383263a0"},{"key":"2026100808351439000_2026.09.21.753242v3.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(00)00162-0"},{"key":"2026100808351439000_2026.09.21.753242v3.22","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-120219-055903"},{"key":"2026100808351439000_2026.09.21.753242v3.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008248107"},{"key":"2026100808351439000_2026.09.21.753242v3.24","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0804439"},{"key":"2026100808351439000_2026.09.21.753242v3.25","doi-asserted-by":"publisher","DOI":"10.1101\/2025.02.11.637707"},{"key":"2026100808351439000_2026.09.21.753242v3.26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-179754"},{"key":"2026100808351439000_2026.09.21.753242v3.27","doi-asserted-by":"crossref","first-page":"e2300001","DOI":"10.1111\/boc.202300001","article-title":"Dynamin-2 controls actin remodeling for efficient complement receptor 3-mediated phagocytosis","volume":"115","year":"2023","journal-title":"Biol Cell"},{"key":"2026100808351439000_2026.09.21.753242v3.28","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12386"},{"key":"2026100808351439000_2026.09.21.753242v3.29","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20839"},{"key":"2026100808351439000_2026.09.21.753242v3.30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2133841100"},{"key":"2026100808351439000_2026.09.21.753242v3.31","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2102"},{"key":"2026100808351439000_2026.09.21.753242v3.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2013.07.036"},{"key":"2026100808351439000_2026.09.21.753242v3.33","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1091\/mbc.e11-02-0114","article-title":"Evidence for a fence that impedes the diffusion of phosphatidylinositol 4,5-bisphosphate out of the forming phagosomes of macrophages","volume":"22","year":"2011","journal-title":"MBoC"},{"key":"2026100808351439000_2026.09.21.753242v3.34","doi-asserted-by":"crossref","first-page":"e34798","DOI":"10.7554\/eLife.34798","article-title":"Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated phagosomes","volume":"7","year":"2018","journal-title":"eLife"},{"key":"2026100808351439000_2026.09.21.753242v3.35","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-05-0494"},{"key":"2026100808351439000_2026.09.21.753242v3.36","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.1.61"},{"key":"2026100808351439000_2026.09.21.753242v3.37","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00002.2012"},{"key":"2026100808351439000_2026.09.21.753242v3.38","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200909025"},{"key":"2026100808351439000_2026.09.21.753242v3.39","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.7.1353"},{"key":"2026100808351439000_2026.09.21.753242v3.40","first-page":"62","article-title":"Perfect and Near-Perfect Adaptation in Cell Signaling","volume":"2","year":"2016","journal-title":"cels"},{"key":"2026100808351439000_2026.09.21.753242v3.41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.16.10983"},{"key":"2026100808351439000_2026.09.21.753242v3.42","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1182\/blood.V90.8.3187","article-title":"Increased Phagocyte Fc\u03b3RI Expression and Improved Fc\u03b3-Receptor\u2013Mediated Phagocytosis After In Vivo Recombinant Human Interferon-\u03b3 Treatment of Normal Human Subjects","volume":"90","year":"1997","journal-title":"Blood"},{"key":"2026100808351439000_2026.09.21.753242v3.43","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.4049\/jimmunol.124.5.2436","article-title":"Interferon enhances the expression of Fc gamma receptors","volume":"124","year":"1980","journal-title":"The Journal of Immunology"},{"key":"2026100808351439000_2026.09.21.753242v3.44","doi-asserted-by":"crossref","unstructured":"ImmGen Consortium, Open-source ImmGen: mononuclear phagocytes. Nat Immunol 17, 741 (2016).","DOI":"10.1038\/ni.3478"},{"key":"2026100808351439000_2026.09.21.753242v3.45","doi-asserted-by":"publisher","DOI":"10.1023\/B:IFLA.0000014708.87440.45"},{"key":"2026100808351439000_2026.09.21.753242v3.46","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20230277"},{"key":"2026100808351439000_2026.09.21.753242v3.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2024.102368"},{"key":"2026100808351439000_2026.09.21.753242v3.48","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1543"},{"key":"2026100808351439000_2026.09.21.753242v3.49","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90401-8"},{"key":"2026100808351439000_2026.09.21.753242v3.50","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.cels.2020.02.005","article-title":"A Live-Cell Screen for Altered Erk Dynamics Reveals Principles of Proliferative Control","volume":"10","year":"2020","journal-title":"Cell Systems"},{"key":"2026100808351439000_2026.09.21.753242v3.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.039"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.21.753242","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:35:31Z","timestamp":1791473731000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.21.753242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":51,"URL":"https:\/\/doi.org\/10.64898\/2026.09.21.753242","relation":{},"subject":[],"published":{"date-parts":[[2026,9,27]]},"subtype":"preprint"}}