Ruth Marian Guzman-Genuino1,2,3, Tanya Dimova3,4, Yuan You3, Paulomi Aldo3, John D Hayball1,2, Gil Mor3,5, Kerrilyn R Diener1,2. 1. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia. 2. Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia. 3. Yale School of Medicine, Yale University, New Haven, CT, USA. 4. Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Sofia, Bulgaria. 5. C.S. Mott Center for Human Growth and Development, Wayne State University, Detroit, MI, USA.
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.
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.
Authors: L G De Oliveira; G E Lash; C Murray-Dunning; J N Bulmer; B A Innes; R F Searle; N Sass; S C Robson Journal: Placenta Date: 2010-05-18 Impact factor: 3.481
Authors: Ruth Marian Guzman-Genuino; Preethi Eldi; Pablo Garcia-Valtanen; John D Hayball; Kerrilyn R Diener Journal: Front Immunol Date: 2019-12-11 Impact factor: 7.561
Authors: Yuan You; Patrick Stelzl; Dana N Joseph; Paulomi B Aldo; Anthony J Maxwell; Nava Dekel; Aihua Liao; Shannon Whirledge; Gil Mor Journal: Front Immunol Date: 2021-11-01 Impact factor: 7.561