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

Am J Reprod Immunol. 2019 Sep;82(3):e13154. doi: 10.1111/aji.13154. Epub 2019 Jun 18.

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/naïve, 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/naïve 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/naïve 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/naïve 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/naïve B cells in particular, are retained in the intervillous blood in response to certain chemokines produced by the placenta during late healthy pregnancy.

Keywords: B cells; B-cell maturation; chemokines; intervillous blood; placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Separation
  • Cells, Cultured
  • Chemokine CCL20 / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Immune Tolerance
  • Lymphopoiesis
  • Placenta / immunology*
  • Pregnancy
  • Receptors, CCR6 / metabolism

Substances

  • CCR6 protein, human
  • Chemokine CCL20
  • Receptors, CCR6