Stromal cell regulation of lymphoid and myeloid differentiation.
In vitro microenvironmental influences seem to be critical for both B lymphocyte and myeloid differentiation. Studies on murine Dexter cultures and Whitlock-Witte lymphocyte cultures suggest the presence of two critical stromal regulatory cells: an alkaline-phosphatase-positive epithelioid cell and a macrophage. Further data suggest that these cells are capable of producing colony stimulating factor-1, granulocyte-macrophage CSF, a myeloid synergizing activity, and probably separate B cell growth factors. Isolation of a cell line from Dexter stroma was accomplished and this line produced CSF-1, GM-CSF, a pre-B cell and myeloid synergizing activity, and an activity acting on differentiated B cells. We speculate that the Dexter and Whitlock-Witte in vitro culture systems are regulated by factors produced by the two adherent cell types. A lineage nonspecific factor capable of inducing cells into the B lineage or synergizing with interleukin-3, GM-CSF, and CSF-1 is produced, which presumably acts on early stem cells. In addition, the cell line produces GM-CSF, CSF-1, and a factor acting on differentiated B cells. We speculate that in these culture systems, these "terminal differentiating hormones" regulate the final pathway of differentiation, whereas the pre-B-synergizing activity supports early stem cells that can then respond to the other differentiating hormones.
Quesenberry
P J
PJ
University of Virginia, School of Medicine, Charlottesville 22908.
McNiece
I K
IK
Robinson
B E
BE
Woodward
T A
TA
Baber
G B
GB
McGrath
H E
HE
Isakson
P C
PC
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D006133:Growth Substances / Q000096:biosynthesis / Q000494:pharmacology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D009924:Organ Culture Techniques
D006133:Growth Substances