In vivo and in vitro suppression of primary B lymphocytopoiesis by tumor-derived and recombinant granulocyte colony-stimulating factor.

Abstract

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.

• Authors: M Y Lee, K L Fevold, K Dorshkind, R Fukunaga, S Nagata, C Rosse
• Journal: Blood (Blood) Vol. 82 Issue 7 Pg. 2062-8 (Oct 01 1993) ISSN: 0006-4971 [Print] United States
• PMID: 7691247 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Culture Media, Conditioned
• Interleukin-7
• Recombinant Proteins
• Granulocyte Colony-Stimulating Factor

Topics

• Animals
• B-Lymphocytes (cytology, drug effects)
• Bone Marrow (drug effects, pathology)
• Bone Marrow Cells
• Cells, Cultured
• Culture Media, Conditioned
• Female
• Flow Cytometry
• Granulocyte Colony-Stimulating Factor (biosynthesis, isolation & purification, pharmacology)
• Hematopoietic Stem Cells (cytology, drug effects)
• Immunosuppression Therapy
• Interleukin-7 (pharmacology)
• Male
• Mammary Neoplasms, Experimental (metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Recombinant Proteins (pharmacology)