The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 129, 483-505, Copyright © 1969 by The Rockefeller University Press


ARTICLE

PATHOGENESIS OF CHRONIC DISEASE ASSOCIATED WITH PERSISTENT LYMPHOCYTIC CHORIOMENINGITIS VIRAL INFECTION : I. RELATIONSHIP OF ANTIBODY PRODUCTION TO DISEASE IN NEONATALLY INFECTED MICE



Michael B. A. Oldstone M.D.1 and Frank J. Dixon M.D.1

1 From the Department of Experimental Pathology, Scripps Clinic and Research Foundation, La Jolla, California 92037

Mice infected shortly after birth with lymphocytic choriomeningitis (LCM) virus are not immunologically tolerant, although they carry the virus throughout life. These LCM carrier mice make anti-LCM antibody, which apparently complexes with viral antigen in the circulation and these complexes accumulate in the glomeruli.

LCM carrier mice of different strains vary significantly as to concentration of detectable infectious virus in their tissue, amount and time of appearance of anti-LCM antibody, and development of an associated chronic disease. The chronic disease consists primarily of glomerulonephritis, focal hepatic necrosis, and disseminated lymphoid infiltrations. LCM carriers of the SWR/J strain contain high tissue concentrations of virus, considerable anti-LCM antibody detectable in the glomeruli by 3 wk to 2 months of age and develop chronic disease within the first 2–3 months of life. In contrast, C3H strain LCM carriers contain 1/1000 as much infectious virus, less detectable anti-LCM antibody, and have not, over a 24 month observation period, developed any detectable disease. B10D2 old and new carrier mice with intermediate amounts of virus develop chronic disease during the latter half of the first year of life.

The pathogenesis of the glomerulonephritis of chronic LCM disease is apparently related to the formation of circulating virus-antibody complexes which are trapped in the glomerular filter. There is no evidence for direct glomerular injury by the virus nor for any autoimmune response by the host.

Submitted on October 22, 1968


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