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

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...

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Published in:International journal of molecular medicine 2015-05, Vol.35 (5), p.1273-1289
Main Authors: ISHIKAWA, TOMOKO, TAKIZAWA, TAKAMI, IWAKI, JUN, MISHIMA, TAKUYA, UI-TEI, KUMIKO, TAKESHITA, TOSHIYUKI, MATSUBARA, SHIGEKI, TAKIZAWA, TOSHIHIRO
Format: Article
Language:English
Subjects:
Endothelium
Fcγ region receptor IIb
Fetuses
human placenta
Immunity
Immunoglobulin G
Immunoglobulins
maternal IgG
Medical research
Medicine, Experimental
Physiological aspects
Placenta
placental endothelial cells
Plasmids
Proteins
RAS-related protein Rab-3D
Studies
Umbilical cord
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Summary: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.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2015.2141