Journal
STEM CELL REPORTS
Volume 6, Issue 1, Pages 137-149Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2015.11.011
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Funding
- Herzenberg Laboratory
- NIAID/NIH [HHSN272201400002C]
- National Cancer Institute [P30 CA 82103]
- UCSF Helen Diller Family Comprehensive Cancer Center CFAR Supplement Award
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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.
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