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Title: Association of murine lupus and thymic full-length endogenous retroviral expression maps to a bone marrow stem cell

Recent studies of thymic gene expression in murine lupus have demonstrated 8.4-kb (full-length size) modified polytropic (Mpmv) endogenous retroviral RNA. In contrast, normal control mouse strains do not produce detectable amounts of such RNA in their thymuses. Prior studies have attributed a defect in experimental tolerance in murine lupus to a bone marrow stem cell rather than to the thymic epithelium; in contrast, infectious retroviral expression has been associated with the thymic epithelium, rather than with the bone marrow stem cell. The present study was designed to determine whether the abnormal Mpmv expression associated with murine lupus mapped to thymic epithelium or to a marrow precursor. Lethally irradiated control and lupus-prone mice were reconstituted with T cell depleted bone marrow; one month later their thymuses were studied for endogenous retroviral RNA and protein expression. Recipients of bone marrow from nonautoimmune donors expressed neither 8.4-kb Mpmv RNA nor surface MCF gp70 in their thymuses. In contrast, recipients of bone marrow from autoimmune NZB or BXSB donors expressed thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70. These studies demonstrate that lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells.
Authors:
; ;  [1]
  1. (National Institutes of Health, Bethesda, MD (USA))
Publication Date:
OSTI Identifier:
5760970
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Immunology; (USA); Journal Volume: 146:9
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; LUPUS; GENE REGULATION; STEM CELLS; BIOLOGICAL FUNCTIONS; BONE MARROW; EPITHELIUM; MICE; RADIATION CHIMERAS; RNA; THYMUS; VIRUSES; ANIMAL CELLS; ANIMAL TISSUES; ANIMALS; BACTERIAL DISEASES; BODY; CHIMERAS; DISEASES; HEMATOPOIETIC SYSTEM; IMMUNE SYSTEM DISEASES; INFECTIOUS DISEASES; LYMPHATIC SYSTEM; MAMMALS; MICROORGANISMS; MOSAICISM; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PARASITES; RODENTS; SOMATIC CELLS; TISSUES; TUBERCULOSIS; VERTEBRATES 560152* -- Radiation Effects on Animals-- Animals