Ordering human CD34+CD10−CD19+pre/pro-B-cell and CD19−common lymphoid progenitor stages in two pro-B-cell development pathways
| Autor: | Antonio de-la-Hera, Norman Muñoz-A., Ana van-den-Rym, Melchor Alvarez-Mon, Pedro Escoll, Jorge Monserrat, Eva Sanz, Ismael Ranz |
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| Rok vydání: | 2010 |
| Předmět: |
Antigens
CD19 B-Lymphocyte Subsets Gene Rearrangement B-Lymphocyte Heavy Chain CD34 Antigens CD34 Bone Marrow Cells CD19 Mice immune system diseases hemic and lymphatic diseases Leukemia B-Cell medicine Animals Humans Lymphopoiesis Progenitor cell B cell Cell Proliferation Multidisciplinary Base Sequence biology Gene Expression Profiling Precursor Cells B-Lymphoid Infant Newborn Models Immunological Cell Differentiation DNA Lymphoid Progenitor Cells Biological Sciences Fetal Blood Coculture Techniques Cell biology Gene expression profiling medicine.anatomical_structure Immunology biology.protein Neprilysin PAX5 Bone marrow Stromal Cells |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:5925-5930 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Studies here respond to two long-standing questions: Are human “pre/pro-B” CD34+CD10−CD19+and “common lymphoid progenitor (CLP)/early-B” CD34+CD10+CD19−alternate precursors to “pro-B” CD34+CD19+CD10+cells, and do the pro-B cells that arise from these progenitors belong to the same or distinct B-cell development pathways? Using flow cytometry, gene expression profiling, and Ig VH-D-JHsequencing, we monitor the initial 10 generations of development of sorted cord blood CD34highLineage−pluripotential progenitors growing in bone marrow S17 stroma cocultures. We show that (i) multipotent progenitors (CD34+CD45RA+CD10−CD19−) directly generate an initial wave of Pax5+TdT−“unilineage” pre/pro-B cells and a later wave of “multilineage” CLP/early-B cells and (ii) the cells generated in these successive stages act as precursors for distinct pro-B cells through two independent layered pathways. Studies by others have tracked the origin of B-lineage leukemias in elderly mice to the mouse B-1a pre/pro-B lineage, which lacks the TdT activity that diversifies the VH-D-JHIg heavy chain joints found in the early-B or B-2 lineage. Here, we show a similar divergence in human B-cell development pathways between the Pax5+TdT−pre/pro-B differentiation pathway that gives rise to infant B-lineage leukemias and the early-B pathway. |
| Databáze: | OpenAIRE |
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