In vivo and in vitro suppression of primary B lymphocytopoiesis by
tumor-derived and recombinant granulocyte colony-stimulating factor
MY Lee, KL Fevold, K Dorshkind, R Fukunaga, S Nagata and C Rosse
Department of Biological Structure, University of Washington School of
Medicine, Seattle 98195.
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.
Volume 82,
Issue 7,
pp. 2062-2068,
10/01/1993
Copyright © 1993 by The American Society of Hematology
