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Mature naive B cells are retained in the placental intervillous blood and positively associate with specific chemokines in full-term healthy pregnancy

Journal article
Authors M. Solders
Anna-Carin Lundell
L. Gorchs
S. Gidlof
E. Tiblad
H. Kaipe
Published in American Journal of Reproductive Immunology
Volume 82
Issue 3
ISSN 1046-7408
Publication year 2019
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Language en
Links dx.doi.org/10.1111/aji.13154
Keywords B cells, B-cell maturation, chemokines, intervillous blood, placenta, subsets, reconstitution, lymphopoiesis, memory, fetus, Immunology, Reproductive Biology
Subject categories Obstetrics, Gynecology and Reproductive Medicine, Immunology in the medical area

Abstract

Problem Circulating B-cell numbers are lower during pregnancy compared with non-pregnant women, but the underlying reasons for this are unknown. Pregnancy-related hormones could influence B-cell lymphopoiesis in the bone marrow, but B cells may also be recruited to the placenta. To investigate the latter, we examined whether the proportions of total B cells and B cells at different maturational stages in placental intervillous blood (IVB) differ compared with peripheral blood (PB). Method of study From 23 paired samples of PB and IVB following full-term healthy pregnancies, total B cells and immature/transitional, mature/naive, and memory B cells were identified by flow cytometry. Chemokine levels in blood were analyzed using a Luminex assay. Placental explant-derived supernatant was assayed for B-cell chemotactic activity. Results The proportions of total B cells and mature/naive B cells were significantly higher in IVB relative to PB, while the fractions of immature/transitional cells and memory B cells were higher in PB. Multivariate factor analysis demonstrated that a specific chemokine profile in IVB, including CCL20, positively associated with higher proportions of mature/naive B cells in the intervillous space. All B cells expressed CCR6, the corresponding receptor for CCL20, but the intensity of CCR6 expression was significantly higher in mature/naive B cells relative to immature/transitional B cells. Migration assays showed that placental explant-derived supernatants attract B cells. Conclusion These results indicate that B cells, and mature/naive B cells in particular, are retained in the intervillous blood in response to certain chemokines produced by the placenta during late healthy pregnancy.

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