Association between nuclear antigens and endogenous retrovirus in the generation of autoantibody responses in murine lupus

Autor: Christina L. Roark, Marie-Laure Santiago-Raber, Brian L. Kotzin, Rebecca M. Tucker, Shozo Izui
Rok vydání: 2004
Předmět:
Autoantibodies/*biosynthesis
viruses
Retroviridae Proteins
Oncogenic
Endogenous retrovirus
ddc:616.07
urologic and male genital diseases
medicine.disease_cause
Autoimmunity
Mice
Retrovirus
Viral Envelope Proteins
immune system diseases
Murine leukemia virus
Immunology and Allergy
Pharmacology (medical)
skin and connective tissue diseases
Immunoglobulin G/immunology
Lupus Vulgaris/genetics/*immunology/*virology
Lupus Vulgaris
Mice
Inbred NZB
Antibodies
Monoclonal
Antigens
Nuclear
Chromatin/immunology
Chromatin
medicine.drug_class
Immunology
chemical and pharmacologic phenomena
Enzyme-Linked Immunosorbent Assay
Biology
Cross Reactions
Retroviridae/immunology
Viral Envelope Proteins/immunology
Monoclonal antibody
Rheumatology
Antigen
medicine
Retroviridae Proteins
Oncogenic/immunology
Animals
Autoantibodies
Antigens
Nuclear/*metabolism
Autoantibody
biology.organism_classification
Virology
Retroviridae
Immunoglobulin G
Retroviridae Infections/*immunology
Antibody Formation
Immunization
Retroviridae Infections
Zdroj: Arthritis and Rheumatism, Vol. 50, No 11 (2004) pp. 3626-3636
ISSN: 0004-3591
Popis: Objective (NZB × NZW)F1 (NZB/NZW) mice and other strains of mice with experimental lupus frequently produce autoantibodies to both chromatin constituents and murine leukemia virus envelope gp70. These autoantibody responses are involved in the glomerulonephritis that develops in these mice. This study was undertaken to explore possible connections between these 2 antigen systems. Methods We used monoclonal antibodies (mAb) derived from unmanipulated NZB/NZW mice to investigate the specificity of anti-gp70 and antichromatin autoantibodies for chromatin constituents, recombinant gp70, NZB retroviruses, and retrovirally infected cells. NZB mice were also immunized with retroviral particles and followed up for study of autoantibody responses. Results Spontaneous autoantibody production in NZB/NZW mice reflects high-level autoimmune responses to nuclear antigens and gp70 that do not cross-react with the other antigen. However, both types of autoantibodies have the capability to bind to the endogenous xenotropic virions NZB-X1 or NZB-X2. The mAbs to recombinant gp70 cross-reacted only with the NZB-X2 virus, whereas the antichromatin mAb frequently bound to both retroviruses. The binding of antichromatin autoantibodies was mediated by nuclear material complexed to the retrovirus, and studies showed that this material can be acquired through the budding process. Immunization with NZB-X1 or NZB-X2 virions induced strong responses to gp70 and was much more effective than chromatin at inducing autoantibody responses to chromatin and double-stranded DNA in NZB mice. Conclusion These studies suggest that retroviral virions may harbor nuclear antigens and may link together the autoimmune responses to the disparate antigens, chromatin and gp70.
Databáze: OpenAIRE
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