Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1α-deficient chimeric mice
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Immune cells are exposed to low oxygen tensions as they develop and migrate between blood and different tissues, but the mechanisms by which lymphocytes adapt to hypoxia are poorly understood. Studies reported here of hypoxia-inducible factor 1α (HIF-1α) in lymphocyte development and functions suggest that it has a critical role in regulation of these processes. HIF-1α deficiency in Hif1α −/− → Rag2 −/− chimeric mice results in dramatic and cell lineage-specific defects, which include appearance of abnormal peritoneal B-1-like lymphocytes, with high expression of B220 (CD45) receptor-associated protein tyrosine phosphatase and autoimmunity (accumulation of anti-dsDNA antibodies and rheumatoid factor in serum, deposits of IgG and IgM in kidney and proteinuria) as well as distortions of maturation of B-2 lymphocytes in bone marrow.
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Hypoxia is immunosuppressive for T and B cells of the adaptive immune system (in vivo genetic evidence).
“and the first in vivo genetic evidence that hypoxia is immunosuppressive for T and B cells of the adaptive immune system (37).”
From Targeting HIF-1α abrogates PD-L1–mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues (2022) · cites this paper as [37]
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- Authors
- Kojima, H., Gu, H., Nomura, S., Caldwell, C. C., Kobata, T., Carmeliet, P., Semenza, G. L., & Sitkovsky, M. V.
- Affiliations
- Dokkyo University (JP)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-02-19
- Volume
- 99
- Issue
- 4
- Pages
- 2170-2174
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC122337
- OpenAlex
- W2011846070
- Cited by
- 224
- References
- 26
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 9 · 2019: 8 · 2018: 12 · 2017: 8 · 2016: 13 · 2015: 10 · 2014: 9 · 2013: 7 · 2012: 13
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- hypoxia-inducible factor-1α, B cell development, autoimmunity, hypoxia, chimeric mice, Rag2-deficient mice, anti-dsDNA antibodies, rheumatoid factor, proteinuria, bone marrow, oxygen partial pressure
- MeSH terms
- Animals, B-Lymphocytes, Bone Marrow Cells, Cell Division, DNA-Binding Proteins, Flow Cytometry, Immunohistochemistry, Mice, Inbred C57BL, Mice, Transgenic, Time Factors, Transcription Factors, Autoimmunity, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
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