Abstract
The newborn’s immune system must transition from a sterile haploidentical uterus to the world full of antigens. Regulatory B-cells (Breg; broadly defined as CD19+CD24hiCD38hi) are tolerance promoters in the adult immune system. They can inhibit IFN-γ and IL-17 production by T-cells and are essential in different conditions, including pregnancy. Breg have still not been well characterized in umbilical cord blood, where we hypothesize that they are pivotal in the achievement of tolerance. We studied CD19+CD24hiCD38hi Breg in healthy umbilical cord blood (hUCB) compared to healthy peripheral adult blood (hAPB). Total numbers of Breg were increased in hUCB compared to hAPB (34.39 vs. 9.49%; p = 0.0002), especially in the marginal zone-like B-cell subset, in which the most marked difference could be observed between hUCB and hAPB (60.80 vs. 4.94%; p = 0.1). CD24hiCD38hi subset in hUCB produced IL-10 and inhibited T-cell IFN-γ [1.63 vs. 0.95 stimulation ratio (SR); p = 0.004] and IL-4 (1.63 vs. 1.44 SR; p = 0.39) production. Phenotypically, hUCB Breg cells presented IgMhiIgDhiCD5+CD10+CD27− markers, similar to those described in hAPB Breg cells, but they showed increased IgM concentration and decreased expression of CD22 and CD73 markers. Our work characterized the frequency, phenotype, and function of Breg in hUCB, which may contribute to understanding of immune tolerance during pregnancy, paving the way to a new approach to immune-related diseases in the fetus and the newborn.
Highlights
Avoidance of unwanted immune responses through peripheral tolerance involves several regulatory/suppressor molecules and cell types
We explored the regulatory function of healthy umbilical cord blood (hUCB) B-cells by studying CD3−CD19+CD24hiCD38hi cell subset because it is a heterogeneous population, most B regulatory cell (Breg) cells lie in this compartment
This study presents the functional and phenotypical characterization of the increased Breg cell subset in hUCB defined as CD19+CD24hiCD38hi cells
Summary
Avoidance of unwanted immune responses through peripheral tolerance involves several regulatory/suppressor molecules and cell types. Regulatory B (Breg)-cells are a rare B-cell subpopulation with this regulatory/suppressor function. Several markers have been described for the detection and sorting of these cells. This is nicely reviewed by Rosser and Mauri [1]. Breg Cells in Human Cord Blood to perform their suppressive action by IL-10/TGF-β production, cell-to-cell contact by CD80/86 interaction with T-cells, and CD73-dependent adenosine production [1,2,3,4,5,6]. CD24hiCD38hi and CD24hiCD27+ have been used recently for the study of Bregs in pregnant women [7]
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