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Stem Cell Reports. 2017 Nov 14;9(5):1501-1515. doi: 10.1016/j.stemcr.2017.10.003. Epub 2017 Nov 5.

Detection of Retinal Pigment Epithelium-Specific Antibody in iPSC-Derived Retinal Pigment Epithelium Transplantation Models.

Author information

1
Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: sunaoph@cdb.riken.jp.
2
Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
3
Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
4
Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School of Medicine and Dental Sciences, Tokyo, Japan.
5
Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Ophthalmology, Kawasaki Medical School, Okayama, Japan.
6
Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Kanagawa, Japan.
7
Department of Pathology, Shiga University of Medical Science, Ohtsu, Japan.

Abstract

Antibody-mediated rejection is characterized by donor-specific antibody produced by B cells. However, to our knowledge, B cell invasion and antibody in the inflamed retina after transplantation of retinal pigment epithelial (RPE) cells has not been reported. To determine if RPE transplantation could be performed using allografts, we established in vivo immune rejection models with induced pluripotent stem cell (iPSC)-RPE allografts and determined whether RPE-specific antibody could be detected in these models. We detected alloantibodies in the serum from recipient monkeys that had immune attacks in the retina in an immunofluorescent assay using the transplanted iPSC-RPE cells as the antigen. In addition to T cell and antigen-presenting cell immunity, peripheral blood cells and lymph nodes in animal models with allogeneic iPSC-RPE cells also had activated B cells, which were probably secreting alloantibodies. Using serum and transplanted cells, alloreactive antibody can be detected for the diagnosis of immune rejection after transplantation.

KEYWORDS:

B cells; antibody; immune rejection; induced pluripotent stem cells; retinal pigment epithelial cells

PMID:
29103970
PMCID:
PMC5688231
DOI:
10.1016/j.stemcr.2017.10.003
[Indexed for MEDLINE]
Free PMC Article

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