期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：13
页码：5925-5930
DOI：10.1073/pnas.0907942107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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-JH sequencing, 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-JH Ig 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.
关键词：B1 and B2 cells ; CD19, a Pax5 reporter stepwise acquisition ; layered B-lymphocyte lineages ; single-cell gene and protein expression profiles ; umbilical cord blood
