Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1α-deficient chimeric mice

被引：188

作者：

Kojima, H

Gu, H

Nomura, S

Caldwell, CC

Kobata, T

Carmeliet, P

Semenza, GL

Sitkovsky, MV

机构：

[1] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA

[2] Dokkyo Univ, Sch Med, Inst Med Sci, Div Immunol, Mibu, Tochigi 3210293, Japan

[3] Katholieke Univ Leuven, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium

[4] Johns Hopkins Univ, Sch Med, Inst Genet Med, Baltimore, MD 21287 USA

[5] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA

[6] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2002年 / 99卷 / 04期

关键词：

D O I：

10.1073/pnas.052706699

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

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收藏

页码：2170 / 2174

页数：5

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