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 high incidence when maintained in conventional or specific pathogen-free environments. Cells obtained from the lesions were relatively monomorphic, expressed a variety of B cell associated markers (BP-1, B220, CD43) but lacked surface Ig. Some mice, showed expanded populations of cells phenotypically similar to the recently reported bipotent B/macrophage stem cell subset (AA4.1high, B220-, Ig-) which could be cloned and maintained in vitro. These cells expressed IL-7 receptors, proliferated in response to IL-7 and in most cases had germline configuration of the Ig heavy chain locus. Cell lines cloned from two such tumours generated macrophages spontaneously in culture, consistent with their bipotent B cell/macrophage phenotype. These results suggest that IL-7 plays a role in very early stages of B cell ontogeny prior to bona fide B cell commitment.
Fisher
A G
AG
MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Burdet
C
C
Bunce
C
C
Merkenschlager
M
M
Ceredig
R
R
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D003433:Crosses, Genetic; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation; D015322:Gene Rearrangement, B-Lymphocyte; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008223:Lymphoma / Q000235:genetics / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology; D008264:Macrophages; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010587:Phagocytosis; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013047:Specific Pathogen-Free Organisms; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D015851:Interleukin-7; D011993:Recombinant Fusion Proteins