Impaired Ability of Bone Marrow Stromal Cells to Support B-Lymphopoiesis With Age
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B-lymphopoiesis decreases with age. We studied how aging affects bone marrow stromal cells, because they provide the growth factors and cell contacts required for B-lymphopoiesis. No differences were noted in the cell-surface phenotype of young and old primary-cultured stromal cells. Fluorescence-activated cell sorter-purified stromal cells from old mice were deficient in the ability to support the proliferation of interleukin-7 (IL-7)–specific B-lymphoid cell lines. The kinetics of this response indicated that IL-7 was not immediately available from stromal cells of either age and was further delayed on aged stromal cells. The levels of IL-7 protein within stromal cells were equivalent between young and old animals, suggesting that the production of IL-7 was not altered by aging. Negligible amounts of IL-7 were found either freely secreted or in the extracellular matrix of cultures of young and old marrow. Contact between the lymphoid cells and the primary stromal cells was required for detectable proliferation, suggesting that cell contact was required for the release of IL-7. We propose that stromal cells regulate B-lymphopoiesis by limiting the amount of IL-7 available to the developing precursors. Therefore, we conclude that the age-related decrease in the function of bone marrow stromal cells is related to the impaired release of IL-7.
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Although the number of peripheral B cells decreases with age, a more pronounced decrease of B cells in AD was observed, suggesting that ongoing disease may exacerbate ageing effects.
“Although the number of peripheral B cells decreases with age, a more pronounced decrease of B cells in AD was observed, suggesting that ongoing disease may exacerbate ageing effects [88,89].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [88]
Declines in the bone marrow microenvironment, possibly from reduced IL-7 secretion by stromal cells, have been implicated in B cell lineage aging.
“Declines in the bone marrow microenvironment, possibly as a result of decreased IL-7 secretion by stromal cells, have been implicated in B cell lineage aging (36,37).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [37]
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- Authors
- Stephan, R. P., Reilly, C. R., & Witte, P. L.
- Affiliations
- Loyola University Chicago (US)
- ORCID
- Stephan, Robert P.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1998-01-01
- Volume
- 91
- Issue
- 1
- Pages
- 75-88
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2415706144
- Cited by
- 197
- References
- 52
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 3 · 2013: 7 · 2012: 10
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk048663-03, 1r03ag014218-01)
- National Institute on Aging (AG14218)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK48663)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- mesenchymal stem cells, B cell development, aging, IL-7, lymphocyte proliferation, cell contact, extracellular matrix, bone marrow microenvironment, immunosenescence
- MeSH terms
- Aging, Animals, B-Lymphocytes, Bone Marrow Cells, Cell Communication, Extracellular Matrix, Female, Hematopoiesis, Hematopoietic Stem Cells, Mice, Inbred BALB C, Secretory Rate, Interleukin-7, Stromal Cells, Mice, Knockout, Mice
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