Bone marrow stromal cell regulation of B-lymphopoiesis. I. The role of macrophages, IL-1, and IL-4 in pre-B cell maturation.
Our experiments have addressed regulation of B lymphocyte formation by bone marrow stromal cells. Stromal cells appear to produce a regulatory factor that acts at the pre-B cell stage to induce the expression of Ig L chains and surface Ig. Bone marrow stromal cell conditioned medium was found to contain this factor and the active component was partially purified by HPLC. This stromal cell-derived factor had a m.w. between 16,000 and 20,000, was specifically neutralized by anti-IL-4 mAb, 11B11, and enhanced the proliferation of anti-mu-stimulated B cells. We also found that rIL-4 induced B cell formation in culture. In our studies, IL-1 had no direct effect on pre-B cell maturation, however, IL-1 was found to stimulate the production of IL-4 by both heterogeneous bone marrow stromal cells and a cloned stromal cell line, SCL-160. These effects of IL-1 on factor production by stromal cells were duplicated by the addition of bone marrow-derived macrophages to SCL-160 cells. We conclude that stromal cell-derived IL-4 is a physiologic stimulator for B cell generation. In addition, macrophages appear to play a role in B cell formation by regulating the production of IL-4 by stromal cells via the secretion of IL-1.
King
A G
AG
Department of Pharmacology and Toxicology, West Virginia University Medical Center, Morgantown 26506.
Wierda
D
D
Landreth
K S
KS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media / Q000032:analysis; D005109:Extracellular Matrix / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000502:physiology; D007375:Interleukin-1 / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4; D007378:Interleukins / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology
D000911:Antibodies, Monoclonal; D003470:Culture Media; D007375:Interleukin-1; D007378:Interleukins; D011994:Recombinant Proteins; D015847:Interleukin-4