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

• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1121632109

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.