{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:10:53Z","timestamp":1787735453744,"version":"build-2784847793"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"5","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"MOST | National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFF1000900"],"award-info":[{"award-number":["2023YFF1000900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"MOST | National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0805905"],"award-info":[{"award-number":["2021YFA0805905"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31530070"],"award-info":[{"award-number":["31530070"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:p>In mammals, passive acquisition of maternal immunoglobulins is essential for neonatal immune development and defense against infections. IgG, a central mediator of humoral immunity, is maternally transferred via distinct mechanisms depending on placental structure in placental mammals. In humans (hemochorial placenta), IgG is prenatally transported across the placenta, whereas in large domestic animals such as pigs and cows (epitheliochorial\/connective chorionic placenta), IgG is exclusively transferred postnatally via colostrum and absorbed in the neonatal intestine. Rodents (allantoic chorionic placenta) employ both pathways. Critically, IgG must traverse multiple tissue barriers-including the placenta, mammary gland, and neonatal intestine-to reach the circulation of newborns. While FcRn is known to facilitate IgG transport in the placenta and neonatal intestine, the mechanisms underlying IgG secretion into milk remain unclear. Here, we identify Fc\u03b3RIIB as the key transporter mediating maternal IgG transfer across the mammary gland in mammals. Using constitutive and conditional knockout mice, we demonstrate that Fc\u03b3RIIB deficiency impairs mammary IgG transfer, whereas its overexpression enhances milk IgG levels. Strikingly, in pigs, Fc\u03b3RIIB is highly upregulated in mammary tissue prepartum, and its disruption abolishes IgG accumulation in colostrum. Our work opens avenues for improving neonatal immunity through targeted modulation of Fc\u03b3RIIB-mediated IgG transport.<\/jats:p>","DOI":"10.1073\/pnas.2522841123","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:58:41Z","timestamp":1769619521000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Fc\u03b3RIIB functions as an IgG transporter in the mammary gland"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9747-0741","authenticated-orcid":false,"given":"Xin","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihui","family":"Wan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]},{"name":"College of Forestry, Jiangxi Agricultural University","place":["Nanchang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiren","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhao","family":"Peng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuncun","family":"Ke","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghe","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitang","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4686-3296","authenticated-orcid":false,"given":"Shuyang","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gengsheng","family":"Cao","sequence":"additional","affiliation":[{"name":"Henan Province Livestock Gene Editing Biotechnology Breeding Engineering Center, School of Life Sciences, Henan University","place":["Kaifeng, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Huang","sequence":"additional","affiliation":[{"name":"Henan Province Livestock Gene Editing Biotechnology Breeding Engineering Center, School of Life Sciences, Henan University","place":["Kaifeng, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Pan-Hammarstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8635-9609","authenticated-orcid":false,"given":"Lennart","family":"Hammarstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Capital Agribusiness Future Biotechnology Co., Ltd.","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8681-7684","authenticated-orcid":false,"given":"Mingzhou","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3452-8917","authenticated-orcid":false,"given":"Ran","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9032-8330","authenticated-orcid":false,"given":"Xuguang","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-1465","authenticated-orcid":false,"given":"Dengke","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]},{"name":"Xenotransplantation and Regeneration Key Laboratory of Sichuan Province, Sichuan Clonorgan Biotechnology Co., Ltd.","place":["Neijiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4499-8610","authenticated-orcid":false,"given":"Yaofeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, Frontiers Science Center for Molecular Design Breeding, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.02.014"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abk2189"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.006"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.12.015"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.055"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abh3816"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1898-4"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/immunohorizons.1700057"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2155"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-animal-022516-022818"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-20082-1"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.11.5512"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803247"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.71.2.666"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.85.1.18"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/337184a0"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2003.08.025"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2002.01514.x"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115972"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.12.6246"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199908)29:08<2515::AID-IMMU2515>3.0.CO;2-D"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13328"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/368070a0"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1535455"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-018-01099-1"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2004.06.008"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2006.06.012"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3401"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/379346a0"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0653-x"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2006.01.024"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.4.2331"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.152.2.574"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2015.2141"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00176160"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2427(80)90012-4"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.1.309"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2206"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830261038"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.170.4.1369"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1039\/B711887B"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2006.00457.x"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.05.007"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90846-5"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40104-023-00926-0"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00027-3"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302232"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-018-0509-8"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2762"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119217"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915133107"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202017"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12335"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202250"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01403-0"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-179754"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3582"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.04.005"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2009-2562"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.047"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13393"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2522841123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:58:50Z","timestamp":1769619530000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2522841123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":61,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,2,3]]}},"alternative-id":["10.1073\/pnas.2522841123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2522841123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"assertion":[{"value":"2025-08-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2522841123"}}