In Vivo and In Vitro Suppression of Primary B Lymphocytopoiesis by Tumor-Derived and Recombinant Granulocyte Colony-Stimulating Factor

• Published in: Blood 1993-10, Vol.82 (7), p.2062-2068
• Main Authors: Lee, Minako Y., Fevold, Karen L., Dorshkind, Kenneth, Fukunaga, Rikiro, Nagata, Shigekazu, Rosse, Cornelius
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow - pathology; Bone Marrow Cells; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cells, Cultured; Culture Media, Conditioned; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Granulocyte Colony-Stimulating Factor - biosynthesis; Granulocyte Colony-Stimulating Factor - isolation & purification; Granulocyte Colony-Stimulating Factor - pharmacology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Immunosuppression; Interleukin-7 - pharmacology; Male; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; Mice; Mice, Inbred BALB C; Molecular and cellular biology; Recombinant Proteins - pharmacology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V82.7.2062.2062

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 Whit-lock-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 stromal 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.