Immunopathology of NZB/Bl Mice

Abstract

An ultrastructurally typical virus-like filtrable agent has been recovered from NZB/B1 mice (1); at the same time, preliminary observations have been reported on the activity of the agent in Swiss mice. The present study, an extension of this work, points to two (perhaps related) circumstances which m a y be requisites for the pathogenic action of this agent within and outside the strain N Z B : infection of newborn, or fiffant, mice; persistent, possibly tolerant, infection of adult mice. Methods and MaterialsAnimals.--The care and the methods of study of our colony of NZB/B1 mice, derived from breeding stock provided by Dr. Marianne Bielschowsky and now in the 70th generation of brother-sister matings, are described elsewhere (1, 2).A male CBA/T6 mouse, in a breeding nncleus obtained from Jackson Laboratories (Bar Harbor, Maine) by Dr. Eugene Lance, was crossbred with an NZB/B1 female to obtain the CBA c~ X NZB ~ F1 hybrids.Adult Webster-Swiss mice (Carworth Farms, New City, N. Y.) were used as short-term random breeders to obtain newborn mice. In addition, six pregnant female gnotobiotic CFW mice were obtained from Carworth Farms to lYrovide newborn mice through the courtesy of Mr. Dennis Baker. The digestive microtlora (3) associated with the gnotobiotic colony ineluded lactobacilli, streptococci (Group N), and enterococci. A panel of eight serological tests (to be discussed below) for routine virus antibodies had been performed on 18 of the 72 gnotobiotic CFW mice in the Carworth colony, in each instance with negative results.Adult Swiss mice were obtained frbm a colony (Charles River Farms, North Wilmington, Mass.) known to be free from infection with lymphocytic choriomeningitis (LCM) virus and were used as provisional intermediate hosts in experiments described below.

Wild-Type Gross Leukemia Virus and the Pathogenesis of the Glomerulonephritis of New Zealand Mice

“…The present study revealed the presence of murine leukemia virus (MuLV) CF antigens in extracts of the spleen, liver, and kidneys of (NZB X NZW) FI hybrid mice, as well as NZW and NZB mice, as shown earlier for NZB mice (9). C type murine leukemia virus-like particles have also been found in the corresponding tissues of (NZB X NZW) F1 hybrid mice and NZW mice by electron microscopic study (23; Mellors and Huang, unpublished work), as reported previously for NZB mice (21,(23)(24)(25)(26)(27). The present study further revealed that both GSA and G natural antibody were detectable in the serum of (NZB X NZW) F1 hybrid mice earlier than in NZB mice, and that the 50 % response time for GSA elimination and for proteinuria manifestation of renal glomerular disease occurred in the hybrid mice at 7.3-7.6 months of age.…”

Relative Inability to Induce Tolerance in Adult NZB and NZB/NZW F1 Mice

“…Thus it is worth considering that the immunologic hyperresponsiveness in the NZB and B/W strains and the relative lack of tolerance to protein antigens in all three strains reflect an altered immunologic mechanism(s) ultimately responsible for the development of lymphoid malignancies. Viral particles resembling the C-particles of murine leukemia are present in NZB mice (30). Mice infected with lactic dehydrogenase virus produce antibody to a normally tolerogenic dose of HGG (31).…”

Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir

“…Most of the sequences do not produce functional particles, but it has been noted that all mice with spontaneous autoimmune disease, including NZB (a standard model for hemolytic anemia) and (NZBxNZW) F 1 mice (abbreviated B/W; a standard model for lupus disease), produce large amounts of retrovirus, and the discovery of these viruses was immediately linked to the autoimmunity (8)(9)(10)(11)(12). Although many genetic loci are associated with it, the disease phenotype of B/W mice can be fully recovered in a normal genome when recombined with three loci (13).…”