In vivo and in vitro suppression of primary B lymphocytopoiesis by tumor-derived and recombinant granulocyte colony-stimulating factor.
Transplantation of a granulocytosis-inducing murine CE mammary carcinoma into mice suppresses primary B lymphopoiesis in the marrow. The mechanisms of this tumor-induced B-cell suppression were investigated using Whitlock-Witte-type lymphoid cultures. When seeded with normal marrow progenitors, stromal cells of tumor-bearing mice supported the production of B220+ cells as well as did either stomal cells derived from control mice or the stromal cell line S17. Cultured over normal stroma, marrow cells of tumor-bearing mice depleted of adherent cells and B220+ cells generated B220+ cells as effectively as a similar cell population from control mice. However, interleukin-7-responsive progenitors, were completely depleted from the marrow of tumor-bearing mice. When conditioned medium (CM) of cloned CE tumor cells known to produce granulocyte colony-stimulating factor (G-CSF) and macrophage-CSF, or recombinant murine G-CSF was added to the cultures established with S17 cells, B220+ cell production was significantly diminished. Antiserum to murine G-CSF blocked these effects. These in vitro observations were corroborated by the elimination of marrow B220+ cells in mice injected with G-CSF. These in vitro and in vivo studies suggest that G-CSF plays an inhibitory role in primary B lymphopoiesis by blocking stromal cell-mediated differentiation of early B-cell progenitors into phenotypically recognizable B220+ pre-B cells.
Lee
M Y
MY
Department of Biological Structure, University of Washington School of Medicine, Seattle 98195.
Fevold
K L
KL
Dorshkind
K
K
Fukunaga
R
R
Nagata
S
S
Rosse
C
C
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D007165:Immunosuppression Therapy; D015851:Interleukin-7 / Q000494:pharmacology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology
D017077:Culture Media, Conditioned; D015851:Interleukin-7; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor