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

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 mar...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-04, Vol.109 (14), p.5394-5398
Main Authors: Ghosn, Eliver Eid Bou, Yamamoto, Ryo, Hamanaka, Sanae, Yang, Yang, Herzenberg, Leonard A, Nakauchi, Hiromitsu, Herzenberg, Leonore A
Format: Article
Language:English
Subjects:
adult development
Adult stem cells
Adults
Animal models
Animals
B lymphocytes
B-Lymphocytes - cytology
Biological Sciences
Bone marrow
Bone Marrow Cells - cytology
Cell Lineage
Developmental biology
Evolution
Flow Cytometry
Hematopoietic stem cells
Hematopoietic Stem Cells - cytology
humans
Immune system
Lymphocytes B
Mice
Progenitor cells
Spleen
Stem cells
T lymphocytes
Transplants & implants
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1121632109