B1 lymphocytes develop independently of Notch signaling during mouse embryonic development

Nathalia Azevedo Portilho, Rebecca Scarfo, Elisa Bertesago, Ismail Ismailoglu, Michael Kyba, Michihiro Kobayashi, Andrea Ditadi, Momoko Yoshimoto

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


B1 lymphocytes are a small but unique component of the innate immune-like cells. However, their ontogenic origin is still a matter of debate. Although it is widely accepted that B1 cells originate early in fetal life, whether or not they arise from hematopoietic stem cells (HSCs) is still unclear. In order to shed light on the B1 cell origin, we set out to determine whether their lineage specification is dependent on Notch signaling, which is essential for the HSC generation and, therefore, all derivatives lineages. Using mouse embryonic stem cells (mESCs) to recapitulate murine embryonic development, we have studied the requirement for Notch signaling during the earliest B-cell lymphopoiesis and found that Rbpj-deficient mESCs are able to generate B1 cells. Their Notch independence was confirmed in ex vivo experiments using Rbpj-deficient embryos. In addition, we found that upregulation of Notch signaling induced the emergence of B2 lymphoid cells. Taken together, these findings indicate that control of Notch signaling dose is crucial for different B-cell lineage specification from endothelial cells and provides pivotal information for their in vitro generation from PSCs for therapeutic applications.

Original languageEnglish (US)
Article numberdev199373
JournalDevelopment (Cambridge)
Issue number15
StatePublished - Aug 1 2021

Bibliographical note

Funding Information:
This study is supported by the National Institute of Allergy and Infectious Diseases (R01AI121197 to M.Y.) and by the Fondazione Telethon (Italy) (SR-TIGET Core Grant, Project C4) (A.D.). Deposited in PMC for immediate release.

Publisher Copyright:
© 2021 Company of Biologists Ltd. All rights reserved.


  • B1 cells
  • B2 cells
  • Hematopoietic stem cells
  • Lymphopoiesis
  • Mouse embryonic development
  • Mouse embryonic stem cells
  • Notch signaling


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