Truncation of the Murine Neonatal Fc Receptor Cytoplasmic Tail Does Not Alter IgG Metabolism or Transport In Vivo.
Abstract: The neonatal Fc receptor (FcRn) is involved in IgG metabolism and transport in placental mammals. However, whether FcRn is responsible for IgG transfer from maternal serum to colostrum/milk is controversial. Interestingly, large domestic animals, such as cows, pigs, sheep, and horses, in which passive IgG transfer is exclusively completed via colostrum/milk, all express an FcRn α-chain that is shorter in the cytoplasmic tail (CYT) than its counterparts in humans and rodents. To address whether the length variation has any functional significance, we performed in vitro experiments using the Transwell system with the MDCK cell line stably transfected with various FcRn constructs; these clearly suggested that truncation of the CYT tail caused a polar change in IgG transfer. However, we observed no evidence supporting functional changes in IgG in vivo using mice in which the FcRn CYT was precisely truncated. These data suggest that the length variation in FcRn is not functionally associated with passive IgG transfer routes in mammals.
Copyright © 2018 by The American Association of Immunologists, Inc.
Publication Date: 2018-01-03 PubMed ID: 29298832DOI: 10.4049/jimmunol.1700924Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research examines the role of the neonatal Fc receptor (FcRn) in the metabolism and transport of immunoglobulin G (IgG) antibodies in mammals. The results suggest that variations in the length of the FcRn do not significantly affect the passive transfer of IgG in mammals.
Objective of the Study
- The purpose of the study was to explore the functional significance of length variation in the FcRn α-chain. The FcRn is responsible for the metabolism and transport of IgG in placental mammals. It was hypothesized that length variations in the FcRn might influence IgG transfer from the mother’s serum to colostrum/milk, particularly in large domestic animals like cows, pigs, sheep, and horses where this transfer is exclusively completed via colostrum/milk.
Research Methodology
- In vitro experiments were conducted using the Transwell system with the MDCK cell line, which was stably transfected with various FcRn constructs. The researchers aimed to determine whether a truncated cytoplasmic tail (CYT) of FcRn would cause any changes in IgG transfer.
- Subsequently, in vivo tests were carried out using mice with a precisely truncated FcRn CYT to confirm whether any functional changes could be observed in IgG transfer.
Findings of the Study
- The in vitro tests suggested that the truncation of the CYT tail could indeed cause a polar change in IgG transfer. This was an interesting finding that initially supported the study’s hypothesis.
- However, the in vivo tests contradicted the in vitro results. Mice with a truncated FcRn CYT showed no observable functional changes in IgG transfer.
- Therefore, the results suggest that the length variation in FcRn is not functionally associated with passive IgG transfer routes in mammals, countering the study’s initial hypothesis.
Significance of the Study
- This research contributes to the understanding of IgG transfer in mammals, which is crucial for early immunity in newborn mammals. It negates the assumption that the FcRn’s length variation has a significant effect on the transfer of IgG via colostrum/milk.
- The study’s findings could impact future research related to the FcRn and its role in immunity and the development of therapeutic antibodies.
Cite This Article
APA
Ma Y, Ke C, Wan Z, Li Z, Cheng X, Wang X, Zhao J, Ma Y, Ren L, Han H, Zhao Y.
(2018).
Truncation of the Murine Neonatal Fc Receptor Cytoplasmic Tail Does Not Alter IgG Metabolism or Transport In Vivo.
J Immunol, 200(4), 1413-1424.
https://doi.org/10.4049/jimmunol.1700924 Publication
Researcher Affiliations
- State Key Laboratory of Agrobiotechnology, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, People's Republic of China.
- State Key Laboratory of Agrobiotechnology, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, People's Republic of China.
- State Key Laboratory of Agrobiotechnology, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, People's Republic of China.
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
- State Key Laboratory of Agrobiotechnology, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, People's Republic of China.
- State Key Laboratory of Agrobiotechnology, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, People's Republic of China.
- College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, People's Republic of China; and.
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, People's Republic of China.
- State Key Laboratory of Agrobiotechnology, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, People's Republic of China.
- State Key Laboratory of Agrobiotechnology, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, People's Republic of China; yaofengzhao@cau.edu.cn hanhaitang@cau.edu.cn.
- State Key Laboratory of Agrobiotechnology, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, People's Republic of China; yaofengzhao@cau.edu.cn hanhaitang@cau.edu.cn.
MeSH Terms
- Animals
- Biological Transport / physiology
- Dogs
- Female
- Histocompatibility Antigens Class I / chemistry
- Histocompatibility Antigens Class I / metabolism
- Immunity, Maternally-Acquired / physiology
- Immunoglobulin G / metabolism
- Madin Darby Canine Kidney Cells
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Pregnancy
- Receptors, Fc / chemistry
- Receptors, Fc / metabolism
Citations
This article has been cited 3 times.- Ke C, Ma Y, Pan D, Wan Z, Feng T, Yu D, Liu X, Wang H, Du M, Huang L, Zhang Y, Du L, Wang X, Li K, Yu D, Zhang M, Huang J, Qu J, Ren L, Hu Y, Cao G, Hu X, Wu S, Han H, Zhao Y. FcRn is not the receptor mediating the transfer of serum IgG to colostrum in pigs. Immunology 2021 Aug;163(4):448-459.
- Caballero-Flores G, Sakamoto K, Zeng MY, Wang Y, Hakim J, Matus-Acuña V, Inohara N, Núñez G. Maternal Immunization Confers Protection to the Offspring against an Attaching and Effacing Pathogen through Delivery of IgG in Breast Milk. Cell Host Microbe 2019 Feb 13;25(2):313-323.e4.
- Hong M, Liu M, Zhu F, Zhao D, Liu G, Han T, Fei C, Zeng W, Chen S, Wu Q, Li B, Wu S, Shang Y, Ma H, Zhou S, Xu S, Jin T. FcRn-guided antigen trafficking enhances cancer vaccine efficacy. Cancer Immunol Immunother 2025 Jan 3;74(2):54.
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