ArticleThe Journal of experimental medicine2004
Bone marrow microenvironmental changes underlie reduced RAG-mediated recombination and B cell generation in aged mice.
Article in The Journal of experimental medicine, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.
- Immunosenescence: A systems-level overview of immune cell biology and strategies for improving vaccine responses.Experimental gerontology · 2019Pooled it
- A mutation in PTPN6 associated to emphysema alters B-lymphocyte biology in humans and mice.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- The impact of growth hormone (GH) on immunosenescence: exploring the role of B and T cells.Pituitary · 2026Article
- Metabolic reprogramming and immunosenescence: a new sight for glioma therapy.Frontiers in cell and developmental biology · 2026Review
- Immunosenescence: Shaping the Hematological Narrative in the Era of Aging.Aging and disease · 2025Review
- Immunoporosis: The hidden link between aging immune cells and bone fragility.Journal of orthopaedic translation · 2025Review
- Clinical application of mesenchymal stem cells in immunosenescence: a qualitative review of their potential and challenges.Stem cell research & therapy · 2025Review
- Review
- Immune aging and infectious diseases.Chinese medical journal · 2024Review
- The Dynamics of Antibody Titres Against SARS-CoV-2 in Vaccinated Healthcare Workers: A Systemic Literature Review.Vaccines · 2024Review
- Review
- Age-associated changes in innate and adaptive immunity: role of the gut microbiota.Frontiers in immunology · 2024Review
- Adaptive immunity and atherosclerosis: aging at its crossroads.Frontiers in immunology · 2024Review
- The 3 I's of immunity and aging: immunosenescence, inflammaging, and immune resilience.Frontiers in aging · 2024Review
- Memory B cell development elicited by mRNA booster vaccinations in the elderly.The Journal of experimental medicine · 2023Article
- Inflammation and aging: signaling pathways and intervention therapies.Signal transduction and targeted therapy · 2023Review
- The aging of the immune system and its implications for transplantation.GeroScience · 2023Review
- Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-betNature immunology · 2022Article
- Age-related functional decline of human B cells.Cytotechnology · 2022Article
- Myc-Interacting Zinc Finger Protein 1 (Miz-1) Is Essential to Maintain Homeostasis and Immunocompetence of the B Cell Lineage.Biology · 2022Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
During aging, adaptive immunity is severely compromised, due in part to decreased production of B lymphocytes and loss of immunoglobulin (Ig) diversity. However, the molecular mechanisms that underlie age-associated diminished B cell production remain unclear. Using in vivo labeling, we find that this reduction in marrow pre-B cells reflects increased attrition during passage from the pro-B to pre-B cell pool. Analyses of reciprocal bone marrow chimeras reveal that the magnitude and production rates of pre-B cells are controlled primarily by microenvironmental factors, rather than intrinsic events. To understand changes in pro-B cells that could diminish production of pre-B cells, we evaluated rag2 expression and V(D)J recombinase activity in pro-B cells at the single cell level. The percentage of pro-B cells that express rag2 is reduced in aged mice and is correlated with both a loss of V(D)J recombinase activity in pro-B cells and reduced numbers of pre-B cells. Reciprocal bone marrow chimeras revealed that the aged microenvironment also determines rag2 expression and recombinase activity in pro-B cells. Together, these observations suggest that extrinsic factors in the bone marrow that decline with age are largely responsible for less efficient V(D)J recombination in pro-B cells and diminished progression to the pre-B cell stage.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.