4.6 Article

Human Cord Blood B Cells Differ from the Adult Counterpart by Conserved Ig Repertoires and Accelerated Response Dynamics

Journal

JOURNAL OF IMMUNOLOGY
Volume 206, Issue 12, Pages 2839-2851

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2100113

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Funding

  1. Deutsche Forschungsgemeinschaft [SE1885/2-1, SE1885/2-2, Ku1315/10-1, TRR60, DU1964/1-1]
  2. Deutsche Krebshilfe [70112628]
  3. Swedish Research Council [2017-01118]
  4. Cancerfonden [CAN 2018/710]
  5. Swedish Research Council [2017-01118] Funding Source: Swedish Research Council
  6. Formas [2017-01118] Funding Source: Formas

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Umbilical cord blood B cells exhibit a mature phenotype similar to adult B cells, with diverse yet conserved Ig repertoire and accelerated responsiveness. This suggests that UCB B cells are not immature but differ in their response dynamics compared to adult B cells.
Neonatal and infant immune responses are characterized by a limited capability to generate protective Ab titers and memory B cells as seen in adults. Multiple studies support an immature or even impaired character of umbilical cord blood (UCB) B cells themselves. In this study, we provide a comprehensive molecular and functional comparison of B cell subsets from UCB and adult peripheral blood. Most UCB B cells have a mature, naive B cell phenotype as seen in adults. The UCB Ig repertoire is highly variable but interindividually conserved, as BCR clonotypes are frequently shared between neonates. Furthermore, UCB B cells show a distinct transcriptional program that confers accelerated responsiveness to stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into Ab-secreting cells, presumably limiting memory B cell formation. Humanized mice suggest that the distinctness of UCB versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice, albeit our findings suggest only partial comparability to murine B-1 cells. Our study shows that UCB B cells are not immature or impaired but differ from their adult mature counterpart in a conserved BCR repertoire, efficient IgA class switching, and accelerated, likely transient response dynamics.

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