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The role of splenic colony-forming units in autoimmune disease
1Cellular Immunology Section, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, Bethesda, Maryland 20892.
Stem cell activity in murine lupus was investigated by analyzing endogenous splenic colony-forming units in sublethally irradiated inbred, congenic, and consomic mice as well as F1 crosses. Splenic colony-forming units (CFU-s) were elevated (greater than 100) in young NZB mice as compared with nonautoimmune-prone mice (less than 10). In lpr/lpr and gld/gld mice, elevated levels of CFU-s were in association with disease manifestations. F1 crosses of inbred lpr/lpr mice often showed an excess of CFU-s in females when compared with male littermates. The autoimmunity accelerating factor on the Y chromosome of BXSB mice led to high numbers of CFU-s relative to female littermates. The xid gene, which does not alter stem cell activity but, instead, interferes with terminal lymphocyte maturation, had no effect on CFU-s in congenic mice. These studies demonstrate that there is a strong association between increased numbers of CFU-s and the development of generalized autoimmunity; increased stem cell division may be important for the development of murine lupus.
Stem cell activity in murine lupus was investigated by analyzing endogenous splenic colony-forming units in sublethally irradiated inbred, congenic, and consomic mice as well as F1 crosses. Splenic colony-forming units (CFU-s) were elevated (greater than 100) in young NZB mice as compared with nonautoimmune-prone mice (less than 10). In lpr/lpr and gld/gld mice, elevated levels of CFU-s were in association with disease manifestations. F1 crosses of inbred lpr/lpr mice often showed an excess of CFU-s in females when compared with male littermates. The autoimmunity accelerating factor on the Y chromosome of BXSB mice led to high numbers of CFU-s relative to female littermates. The xid gene, which does not alter stem cell activity but, instead, interferes with terminal lymphocyte maturation, had no effect on CFU-s in congenic mice. These studies demonstrate that there is a strong association between increased numbers of CFU-s and the development of generalized autoimmunity; increased stem cell division may be important for the development of murine lupus.