Haematopoietic cell transfers between C57BL/6 mice differing at the lpr or gld locus.
The generalized lymphoproliferative disease (gld) and lymphoproliferation (lpr) mutations induce the development of strikingly similar autoimmune and lymphoproliferative syndromes in C57BL/6 mice (B6). These syndromes are characterized by hyperglobulinaemia, high levels of circulating autoantibodies and significant splenomegaly and lymphadenopathy resulting principally from the accumulation of a double negative CD4/CD8 T-cell population. These similarities led to the suggestion that the gld and lpr mutations affect two different steps of a common metabolic pathway controlling the differentiation of the T cells. By transferring haematopoietic cells into sublethally irradiated recipients we provide evidence for the different aetiology of the gld- and lpr-induced syndromes. The [gld----gld] chimaeras developed a gld-induced syndrome, like the [lpr----lpr] chimaeras developed a lpr-induced syndrome. However, in contrast to the severe lymphoid aplasia observed in the [lpr----wild] chimaeras, the [gld----wild] chimaeras showed an attenuated form of the gld-induced syndrome. The [lpr----gld] chimaeras developed a lymphoid aplasia (as in the [lpr----wild] chimaeras). This result shows that the gld environment cannot substitute for the lpr environment and allow for the emergence of an lpr-induced pathology.
Sandoz Pharma AG, Preclinical Research Basel, Switzerland.
E M
EM
Montecino-Rodriguez
F
F
Loor
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D008070:Lipopolysaccharides / Q000276:immunology; D008198:Lymph Nodes / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics*; D009154:Mutation; D011828:Radiation Chimera / Q000276:immunology; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
D008070:Lipopolysaccharides; D003208:Concanavalin A