Early-life human lymphopoiesis generates a distinct B-cell lineage
- 1Emory University
Abstract
We characterize the first wave of human B-lymphopoiesis across gestation (n=42 donors) and identify a developmentally and functionally distinct B-cell lineage that shapes antibody specificity before birth. The earliest lymphoid progenitors engage an evolutionarily conserved genetic program enriched for imprinted genes associated with embryogenesis in mice and humans. These progenitors arise in the yolk sac and acquire Early B-cell Factor 1 (EBF1) in the embryonic liver, initiating B-lymphopoiesis before Hematopoietic Stem Cells emerge. Functionally, these early-life B-lymphoid progenitors (eBLPs; CD81hiTdT-IL3R+) respond to IL-3 to promote B-cell fate commitment and generate two waves of stereotyped public B-cell receptor (BCR) repertoires, shaping adaptive immunity at birth. The same molecular program and public BCRs are recapitulated during B-cell differentiation from pluripotent stem cells in vitro and after transplantation into humanized mice, where they generate antibody-secreting cells and SOX4+ B cells resembling infant lymphocytes. Developmental origin therefore intrinsically programs B-cell identity and antibody specificity.
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BibTeX
@misc{nazzari2026earlylife,
title = {{Early-life human lymphopoiesis generates a distinct B-cell lineage}},
author = {A. F. Nazzari and K. Kothari and J. Yang and A. Kosters and P. Chaudhry and I. A. Glass and Birth Defects and Research Laboratory (BDRL) and E. Ghosn},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.756737},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.756737v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Early-life human lymphopoiesis generates a distinct B-cell lineage
AU - A. F. Nazzari
AU - K. Kothari
AU - J. Yang
AU - A. Kosters
AU - P. Chaudhry
AU - I. A. Glass
AU - Birth Defects and Research Laboratory (BDRL)
AU - E. Ghosn
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.756737
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.756737v1
AB - We characterize the first wave of human B-lymphopoiesis across gestation (n=42 donors) and identify a developmentally and functionally distinct B-cell lineage that shapes antibody specificity before birth. The earliest lymphoid progenitors engage an evolutionarily conserved genetic program enriched for imprinted genes associated with embryogenesis in mice and humans. These progenitors arise in the yolk sac and acquire Early B-cell Factor 1 (EBF1) in the embryonic liver, initiating B-lymphopoiesis before Hematopoietic Stem Cells emerge. Functionally, these early-life B-lymphoid progenitors (eBLPs; CD81hiTdT-IL3R+) respond to IL-3 to promote B-cell fate commitment and generate two waves of stereotyped public B-cell receptor (BCR) repertoires, shaping adaptive immunity at birth. The same molecular program and public BCRs are recapitulated during B-cell differentiation from pluripotent stem cells in vitro and after transplantation into humanized mice, where they generate antibody-secreting cells and SOX4+ B cells resembling infant lymphocytes. Developmental origin therefore intrinsically programs B-cell identity and antibody specificity.
ER -