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Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5394-8. doi: 10.1073/pnas.1121632109. Epub 2012 Mar 19.

Distinct B-cell lineage commitment distinguishes adult bone marrow hematopoietic stem cells.

Author information

1
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. eliverg@stanford.edu

Abstract

The question of whether a single hematopoietic stem cell (HSC) gives rise to all of the B-cell subsets [B-1a, B-1b, B-2, and marginal zone (MZ) B cells] in the mouse has been discussed for many years without resolution. Studies here finally demonstrate that individual HSCs sorted from adult bone marrow and transferred to lethally irradiated recipients clearly give rise to B-2, MZ B, and B-1b, but does not detectably reconstitute B-1a cells. These findings place B-2, MZ, and B-1b in a single adult developmental lineage and place B-1a in a separate lineage derived from HSCs that are rare or missing in adults. We discuss these findings with respect to known developmental heterogeneity in other HSC-derived lymphoid, myeloid, and erythroid lineages, and how HSC developmental heterogeneity conforms to the layered model of the evolution of the immune system that we proposed some years ago. In addition, of importance to contemporary medicine, we consider the implications that HSC developmental heterogeneity may have for selecting HSC sources for human transplantation.

PMID:
22431624
PMCID:
PMC3325648
DOI:
10.1073/pnas.1121632109
[Indexed for MEDLINE]
Free PMC Article
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