Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1alpha -deficient chimeric mice.
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 1alpha (HIF-1alpha) in lymphocyte development and functions suggest that it has a critical role in regulation of these processes. HIF-1alpha deficiency in Hif1alpha(-/-) --> 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.
Kojima
Hidefumi
H
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA.
Gu
Hua
H
Nomura
Saeko
S
Caldwell
Charles C
CC
Kobata
Tetsuji
T
Carmeliet
Peter
P
Semenza
Gregg L
GL
Sitkovsky
Michail V
MV
D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics; D005434:Flow Cytometry; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
D004268:DNA-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C499308:Rag2 protein, mouse; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2