Trophoblasts promote induction of a regulatory phenotype in B cells that can protect against detrimental T cell-mediated inflammation

Date

2019

Authors

Guzman-Genuino, R.M.
Dimova, T.
You, Y.
Aldo, P.
Hayball, J.D.
Mor, G.
Diener, K.R.

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Journal article

Citation

American Journal of Reproductive Immunology, 2019; 82(6):e13187-1-e13187-16

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Ruth Marian Guzman‐Genuino, Tanya Dimova, Yuan You, Paulomi Aldo, John D. Hayball, Gil Mor, Kerrilyn R. Diener

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Abstract

PROBLEM:A successful outcome to pregnancy is critically dependent on the initiation of maternal immune tolerance before embryo implantation. Cells of embryonic origin that come in contact with the uterine microenvironment can exert influence over the phenotype and function of immune cells to facilitate robust implantation, however what influence they may have on B cells remains unknown. In this study, we investigate the effect of human trophoblast cells on B cell phenotype and the subsequent effect on peri-implantation events. METHOD OF STUDY:We cultured purified human B cells with the first trimester human trophoblast cell line Swan-71 to investigate trophoblast-B cell interactions and utilized trophoblast spheroids in an in vitro implantation model of migration and invasion. RESULTS:Trophoblast-educated B cells or TE-B cells were found to consist of B cells in committed lineages such as plasmablasts and memory B cells, as well as increased proportions in subsets of CD24hi CD27+ regulatory B cells and CD19+ IL-10+ B cells. Conditioned media from the TE-B cells showed reduced production of pro-inflammatory cytokines that influenced the T cell proliferation and cytokine production. Using trophoblast spheroids, we assessed the role of TE-B cells in trophoblast invasion and migration. Our results demonstrate a protective effect of TE-B conditioned media against deleterious inflammation as evidenced by survival of the trophoblast spheroid in the presence of an immune assault and promotion of a migratory phenotype. CONCLUSION:We posit that trophoblast-mediated education of B cells leads to their acquisition of properties capable of modulating inflammation in the uterine environment during the peri-implantation period. This article is protected by copyright. All rights reserved.

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Link to a related website: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232043, Open Access via Unpaywall

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© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

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