FcγRIIB functions as an IgG transporter in the mammary gland
Abstract
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 FcγRIIB as the key transporter mediating maternal IgG transfer across the mammary gland in mammals. Using constitutive and conditional knockout mice, we demonstrate that FcγRIIB deficiency impairs mammary IgG transfer, whereas its overexpression enhances milk IgG levels. Strikingly, in pigs, FcγRIIB 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 FcγRIIB-mediated IgG transport.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (20)
Xin Li
Lijuan Du
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
Zihui Wan
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
Zhiren Jin
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
Yuanhao Peng
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
Yongliang Fan
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University
Cuncun Ke
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
Yonghe Ma
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
Haitang Han
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
Shuyang Yu
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
Gengsheng Cao
Henan Province Livestock Gene Editing Biotechnology Breeding Engineering Center, School of Life Sciences, Henan University
Tian Huang
Henan Province Livestock Gene Editing Biotechnology Breeding Engineering Center, School of Life Sciences, Henan University
Qiang Pan-Hammarström
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute
Lennart Hammarström
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute
Ning Li
Mingzhou Li
Ran Zhang
Xuguang Du
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
Dengke Pan
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
Yaofeng Zhao
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