LYMPHOPROLIFERATIVE DISORDERS IN IL-7 TRANSGENIC MICE - EXPANSION OF IMMATURE B-CELLS WHICH RETAIN MACROPHAGE POTENTIAL

Transgenic mice carrying the murine IL-7 gene under the MHC class II ( E(alpha)) promoter are described which develop lymphoid tumours at a h igh incidence when maintained in conventional or specific pathogen-fre e environments. Cells obtained from the lesions were relatively monomo rphic, expressed a variety of B cell associated markers (BP-1, B220, C D43) but lacked surface Ig. Some mice showed expanded populations of c ells phenotypically similar to the recently reported bipotent B/macrop hage stem cell subset (AA4.1(high), B220(-), Ig(-)) which could be clo ned and maintained in vitro. These cells expressed IL-7 receptors, pro liferated in response to IL-7 and in most cases had germline configura tion of the Ig heavy chain locus. Cell lines cloned from two such tumo urs generated macrophages spontaneously in culture, consistent with th eir bipotent B cell/macrophage phenotype. These results suggest that I L-7 plays a role in very early stages of B cell ontogeny prior to bona fide a cell commitment.