Fetal Hematopoietic Stem Cell Transplantation Fails to Fully Regenerate the B-Lymphocyte Compartment

• Published in: Stem cell reports 2016-01, Vol.6 (1), p.137-149
• Main Authors: Ghosn, Eliver Eid Bou, Waters, Jeffrey, Phillips, Megan, Yamamoto, Ryo, Long, Brian R., Yang, Yang, Gerstein, Rachel, Stoddart, Cheryl A., Nakauchi, Hiromitsu, Herzenberg, Leonore A.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Lineage - genetics; Cell Lineage - immunology; Cells, Cultured; Embryonic Stem Cells - cytology; Embryonic Stem Cells - immunology; Embryonic Stem Cells - metabolism; Fetal Stem Cells - immunology; Fetal Stem Cells - metabolism; Fetal Stem Cells - transplantation; Fetal Tissue Transplantation - methods; Flow Cytometry; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; Humans; Liver - cytology; Liver - metabolism; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Mice, Inbred C57BL; Mice, Transgenic
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2015.11.011

B cells are key components of cellular and humoral immunity and, like all lymphocytes, are thought to originate and renew from hematopoietic stem cells (HSCs). However, our recent single-HSC transfer studies demonstrate that adult bone marrow HSCs do not regenerate B-1a, a subset of tissue B cells required for protection against pneumonia, influenza, and other infections. Since B-1a are regenerated by transfers of fetal liver, the question arises as to whether B-1a derive from fetal, but not adult, HSCs. Here we show that, similar to adult HSCs, fetal HSCs selectively fail to regenerate B-1a. We also show that, in humanized mice, human fetal liver regenerates tissue B cells that are phenotypically similar to murine B-1a, raising the question of whether human HSC transplantation, the mainstay of such models, is sufficient to regenerate human B-1a. Thus, our studies overtly challenge the current paradigm that HSCs give rise to all components of the immune system. •Purified LT-HSC transplantation fails to fully regenerate the murine immune system•LT-HSC transplants selectively fail to regenerate B-1a cells•LT-HSC transplantation does not regenerate VH11-encoded natural antibodies•Human fetal liver regenerate peritoneal B cells that resemble murine B-1a Ghosn and colleagues show that purified HSC transplantation selectively fails to regenerate B-1a, a subset of B cells known to be required for protection against pneumonia, influenza, and other infections. Moreover, HSC transplantation does not restore a key repertoire (VH11) of natural antibodies, raising the question of whether human HSC transplantation is sufficient to fully regenerate the immune system.