Abstract
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.
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Selected References
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