IgE is expressed on, but not produced by, fetal cells in the human placenta irrespective of maternal atopy

Abstract

The prevalence of atopic diseases in children has increased during the last decades. Atopic symptoms usually appear early in life. This implies an early priming for atopic disease, possibly even at the fetal level. We therefore compared the presence and production of IgE in the local in utero environment during pregnancy in atopic and non-atopic women. Eighty-six women were included in the study. Fifty women were demonstrated to be atopics, based on clinical symptoms of atopic disease together with a positive Phadiatop and/or skin prick test. Placentas from these term pregnancies were obtained. Slices covering the full thickness of the placenta were cut clockwise around the umbilical cord and were analysed with immunohistochemistry. Surprisingly, numerous IgE+ cells, located primarily in the fetal villous stroma, were detected in a majority of the investigated placentas irrespective of the atopy of the mother or maternal or fetal total serum IgE levels. The placental IgE could not be demonstrated to be bound to IgE receptors, but was shown to be bound to fetal macrophages, possibly via FcgammaRI. No evidence was found for local fetal IgE production, although cells producing epsilon transcripts were occasionally detected in the decidua. We describe here the novel finding of numerous IgE+ cells in the human placenta, suggesting an hitherto unknown role for IgE in a successful pregnancy outcome, irrespective of whether or not the mother is atopic.

Fig. 1

Detection of IgE⁺ cells, mast cells and CD38⁺ cells in the placenta. Acetone-fixed cryostat sections of frozen placental tissue (a–b, d, f–g) and umbilical cord (c) were stained with the ABC ELITE method, with anti-IgE MoAb (clone B3102E8, Southern Biotechnology Assoc.) (a–c) or anti-CD38 MoAb (clone AT13/5, Dako) (f-g) or an isotype matched control MoAb (Dako) (d). A counterstain was performed with Mayer’s haematoxylin. Positive cells are seen as brown/red. For the detection of mast cells (e), sections from formalin fixed biopsies were stained with toluidine blue. (a–b) IgE⁺ cells in the fetal part of the placenta in the chorionic villi mesenchyme. There was no difference in placental IgE expression between atopic (a) and non-atopic (b) mothers. (c) An IgE⁺ cell in a umbilical cord section from an atopic mother. (e) A single mast cell (indicated by arrow) present in the chorionic villi region. (f–g) CD38⁺ cells present in the villous part of the placenta, both as scattered cells (f) and present in fetal vessels (g). Magnification ×600.

Fig. 2

IgE⁺ cells in the placenta are HLA-DR⁺. Acetone-fixed cryostat sections of frozen placental biopsies were double-stained with a FITC conjugated anti-HLA-DR MoAb (clone L243, Becton Dickinson) and an unconjugated anti-IgE MoAb (clone B3102E8, Southern Biotechnology Assoc.) revealed by a rhodamine Red-X conjugated secondary antibody. The sections were mounted with glycerol in PBS containing p-phenylenediamine to reduce the fading of staining during microscopy and analysed with a CSLM (Leica Instruments). (a–c) The double-staining of a placental section from an atopic mother shows HLA-DR⁺ (a), IgE⁺ (b) and HLA-DR⁺ IgE⁺ (c) cells in the villous part of the placenta. Magnification ×500.

Fig. 3

Expression of IgE and IgG receptors in the placenta. In order to detect FcɛRI in the placenta, tissue-bound IgE was eluted from the sections by low pH treatment. As control tissue, sections from a biopsy from lesional skin from an atopic dermatitis patient were used. Acetone-fixed cryostat sections were then stained for IgE (clone B3102E8, Southern Biotechnology Assoc.) and FcɛRI (clone 3G6, Upstate Biotechnology) before and after IgE elution, as described in Materials and methods. Staining of placental (a) and skin (e) sections for IgE⁺ cells on slides treated with PBS. The low pH treatment readily elutes IgE from both placenta (b) and skin (f). Staining for the FcɛRI before low pH treatment reveals staining of FcɛRI in skin (g) but not in placenta (c). Staining following IgE elution reveals no FcɛRI⁺ cells in placenta (d) but strong FcɛRI staining in skin (h), magnification ×150. To compare the expression of IgE and FcγRI, acetone-fixed cryostat sections of frozen placental tissue were stained either with anti-IgE (clone B3102E8, Southern Biotechnology Assoc.) or with anti-CD64 mAb (clone 10·1, Dako) with the ABC ELITE method as described in Materials and methods. (i–j) Consecutive sections of the same slice stained with anti-IgE (i) and anti-CD64 (j). Magnification ×600.