Characterization of the Highly Prevalent Regulatory CD24(hi)CD38(hi) B-Cell Population in Human Cord Blood

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(+)CD24(hi)CD38(hi)) 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(+)CD24(hi)CD38(hi) 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). CD24(hi)CD38(hi) 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 IgM(hi)IgD(hi)CD5(+)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.