缺氧诱导因子1α缺陷嵌合小鼠的B淋巴细胞发育异常与自身免疫
Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1alpha -deficient chimeric mice.
作者信息
Kojima Hidefumi, Gu Hua, Nomura Saeko, Caldwell Charles C, Kobata Tetsuji, Carmeliet Peter, Semenza Gregg L, Sitkovsky Michail V
机构信息
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA.
出版信息
Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2170-4. doi: 10.1073/pnas.052706699.
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.
免疫细胞在发育过程中以及在血液和不同组织之间迁移时会暴露于低氧张力环境中，但是淋巴细胞适应缺氧的机制目前仍知之甚少。本文所报道的关于缺氧诱导因子1α（HIF-1α）在淋巴细胞发育和功能方面的研究表明，它在这些过程的调节中起着关键作用。在Hif1alpha(-/-) --> Rag2(-/-)嵌合小鼠中，HIF-1α缺乏会导致显著的、细胞谱系特异性缺陷，其中包括出现异常的腹膜B-1样淋巴细胞，其B220（CD45）受体相关蛋白酪氨酸磷酸酶高表达以及自身免疫（血清中抗双链DNA抗体和类风湿因子的积累、肾脏中IgG和IgM沉积以及蛋白尿），同时骨髓中B-2淋巴细胞成熟也出现异常。
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