Autoimmnne hemolytic anemia (1-3), membranous glomerulonephritis (4-9), systemic connective-tissue disease (7-10), and malignant lymphoma (11,12) develop in aging NZB/B1 mice. The hemolytic (13) and the renal (8) diseases can be induced (within a few weeks and independently) in young NZB/B1 mice by the transplantation of syngeneic adult spleen cells. The malignant lymphomas, which develop in older NZB/B1 mice with already established hemolytic and renal diseases (12), are of two histological types, reticulum cell sarcoma and pleomorphic malignant lymphoma (12). These lymphomas are maintained in our laboratory by serial transplantation within the strain NZB/B1 (9).In recent years, murine leukemias (and lymphomas) of several varieties have been shown to be caused L j viruses (14--18), a circumstance which has led us to ask whether some, or all, of the immunopathological disorders arising in NZB/B1 mice might also be initiated by viruses or other filtrable agents (9). Accordingly, relevant studies were undertaken of the biological activity of cell-free filtrates prepared from NZB/B1 malignant lymphomas; in the course of this investigation viruslike particles were identified by electron microscopy in malignant lymphoid cells and in nonneoplastic cells and tissues of NZB/B1 mice. A brief account of this work follows. Methods and MaterialsAnimals.--The care and the methods of study of our colony of NZB/B1 mice, which was derived from breeding stock provided by Dr. Marianne Bielschowsky, are described elsewhere (6) as are also the cervical lymph node origin and the initial transplantation of reticulum. cell sarcoma (hereinafter also called malignant lymphoma, 93-line) within this strain (12). We also maintain the CBA/T6 strain of mice and Swiss-Webster albino mice.Lymphoma (Cell-Free) Filtrates.--These were prepared from subcutaneous tumors obtained from NZB/BI mice bearing transplants of malignant lymphoma (12), 93-line. In the finally standardized procedure, the tumor tissue was obtained and handled under sterile conditions, minced, and ground in a chilled mortar with pestle and sand to provide a 10 to 20°7o suspension in pH 7.2 buffered isotonic saline. The suspension was centrifuged in a (Servall Super-
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.
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