The Notch genes encode a conserved family of receptors that influence developmental fate in many species. Prior studies have indicated that Notch-1 and Notch-2 signaling influence the development of hematopoietic stems cells and thymocytes, but little is known regarding Notch expression and function in B-lineage cells. We analyzed the expression of Notch receptors and Notch ligands in human B-lineage cells and bone marrow (BM) stromal cells. Notch-1 mRNA and protein is expressed throughout normal B cell development and in leukemic B-lineage cells. In contrast, Notch-2 expression is limited to pre-B cells expressing low levels of surface μ. The Notch ligand Delta is expressed in BM B-lineage cells. The Notch ligand Jagged-1 is not expressed in B-lineage cells, but is expressed in BM stromal cells. These results suggest a model wherein lateral signaling between Notch and Delta on B-lineage cells and/or Notch/Jagged-1 interactions between B-lineage cells and BM stromal cells may regulate human B cell development.
Bibliographical noteFunding Information:
We thank Barbara Ercole for technical assistance, Janet Peller of the University of Minnesota Cancer Center Flow Cytometry Core for cell sorting support, and Diane Hasz and David Lar-gaespada for provision of murine lymphoid tissues/reagents. We deeply appreciate provision of reagents from and discussion with Irv Bernstein (FHCRC, Seattle) and Jon Aster (Brigham and Womens Hospital, Boston). We also thank Sandi Sherman for assistance with the manuscript and members of the LeBien laboratory for helpful discussion. This work was supported by grants R01 CA31685 and R01 CA76055 from the National Institutes of Health, the Graduate School of the University of Minnesota, the Minnesota Medical Foundation, and the Apogee Enterprises Professorship. ASL was the recipient of the Margaret Mitchell Research Scholarship from the American Cancer Society (Minnesota Council). FEB is supported by The Chris P Tkalcevic Foundation for Leukemia Research as a Special Fellow of the Leukemia and Lymphoma Society.
- B cell precursors