A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells

Stem Cell Reports. 2017 Jun 6;8(6):1563-1572. doi: 10.1016/j.stemcr.2017.04.007. Epub 2017 May 4.


Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs). However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC) potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. Remarkably, clonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes.

Keywords: AGM; B lymphocyte; B-1a cell; hematopoietic stem cell; pre-HSC.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, CD / metabolism
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cadherins / metabolism
  • Calcium-Binding Proteins
  • Cells, Cultured
  • Coculture Techniques
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Endothelial Protein C Receptor / metabolism
  • Female
  • Flow Cytometry
  • Guanine Nucleotide Exchange Factors / genetics
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL


  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Cadherins
  • Calcium-Binding Proteins
  • DLL4 protein, mouse
  • Endothelial Protein C Receptor
  • FGD5 protein, mouse
  • Guanine Nucleotide Exchange Factors
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • cadherin 5