The role of splenic colony-forming units in autoimmune disease.

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.