title: Fc gamma receptor IIb participates in maternal IgG trafficking of human placental endothelial cells.
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.
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Takami
authors.initials: T
authors.lastname: Takizawa
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Iwaki
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Mishima
authors.affiliation: Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ui-Tei
authors.affiliation: Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeshita
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takizawa
mesh_terms: D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D017930:Genes, Reporter; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D010920:Placenta / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D057900:Transcytosis; D014162:Transfection; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D017452:Receptors, IgG; D020692:rab3 GTP-Binding Proteins