Fc gamma receptor IIb participates in maternal IgG trafficking of human placental endothelial cells

Ishikawa,Tomoko; Takizawa,Takami; Iwaki,Jun; Mishima,Takuya; Ui-Tei,Kumiko; Takeshita,Toshiyuki; Matsubara,Shigeki; Takizawa,Toshihiro

doi:10.3892/ijmm.2015.2141

Fc gamma receptor IIb participates in maternal IgG trafficking of human placental endothelial cells

Authors:
- Tomoko Ishikawa
- Takami Takizawa
- Jun Iwaki
- Takuya Mishima
- Kumiko Ui-Tei
- Toshiyuki Takeshita
- Shigeki Matsubara
- Toshihiro Takizawa
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Affiliations: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo 113-8602, Japan, Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan, Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo 113-8602, Japan, Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan
Published online on: March 17, 2015 https://doi.org/10.3892/ijmm.2015.2141
Pages: 1273-1289
Copyright: © Ishikawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The human placental transfer of maternal IgG is crucial for fetal and newborn immunity. Low-affinity immunoglobulin gamma Fc region receptor IIb2 (FCGR2B2 or FcγRIIb2) is exclusively expressed in an IgG-containing, vesicle-like organelle (the FCGR2B2 compartment) in human placental endothelial cells; thus, we hypothesized that the FCGR2B2 compartment functions as an IgG transporter. In this study, to examine this hypothesis, we performed in vitro bio-imaging analysis of IgG trafficking by FCGR2B2 compartments using human umbilical vein endothelial cells transfected with a plasmid vector containing enhanced GFP-tagged FCGR2B2 (pFCGR2B2-EGFP). FCGR2B2-EGFP signals were detected as intracellular vesicular structures similar to FCGR2B2 compartments in vivo. The internalization and transcytosis of IgG was significantly higher in the pFCGR2B2-EGFP-transfected cells than in the mock-transfected cells, and the majority of the internalized IgG was co-localized with the FCGR2B2-EGFP signals. Furthermore, we isolated FCGR2B2 compartments from the human placenta and found that the Rab family of proteins [RAS-related protein Rab family (RABs)] were associated with FCGR2B2 compartments. Among the RABs, RAB3D was expressed predominantly in placental endothelial cells. The downregulation of RAB3D by small interfering RNA (siRNA) resulted in a marked reduction in the FCGR2B2-EGFP signals at the cell periphery. Taken together, these findings suggest that FCGR2B2 compartments participate in the transcytosis of maternal IgG across the human placental endothelium and that RAB3D plays a role in regulating the intracellular dynamics of FCGR2B2 compartments.

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