Immunopathology of NZB/Bl Mice

Abstract

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-

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.…”

Clinical aspects of T‐ and B‐lymphocytes in rheumatic diseases

“…Current theory of the etiology of SLE suggests that a latent virus injection might be at least part of the underlying cause (35,36). If we assume that an agent of this type could specifically effect T-cells, several consequences might follow.…”

Immunologic observations on 9 sets of twins either concordant or discordant for SLE

“…In the SLE-like and leukemic illnesses of New Zealand mice, in which the presence of genetic and immunologic factors is established (13), a pathogenetic role of murine type-C R N A viruses is being defined (14)(15)(16). Recent studies have suggested t h e presence of t y p e C viruses and viral antigens in human SLE and leukemic tissues (17-20), although this issue remains unclarified (21 ).…”