Inhibitory effect of interleukin 3 on early development of human B-lymphopoiesis.
Interleukin 3 (IL-3) is known as a stimulator of proliferation and differentiation of non-lymphoid cells, but information about the activity of IL-3 in lymphopoiesis is limited. In the present study, we examined the effect of IL-3 on human B-lymphopoiesis using the co-culture system on a murine stromal cell line, MS-5, with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF). Although a large number of CD45+CD19+ B cells were generated in the co-culture of cord blood CD34+ cells, the addition of IL-3 to the co-culture suppressed the B-cell generation in a dose-dependent manner. In the co-culture, CD34+IL-3 receptor alpha-chain (IL-3Ralpha)+ cells, but not IL-3Ralpha- cells, produced B cells, and IL-3 suppressed the B-cell generation from CD34+IL-3Ralpha+ cells, suggesting that IL-3 exerts an inhibitory effect through the binding to IL-3Ralpha on CD34+ cells. Because the delayed addition of IL-3 and the short-term exposure to IL-3 showed that IL-3 acted as an inhibitor at an early stage of B-cell development from CD34+ cells, before the generation of CD19+ B cells, the effect of IL-3 on the early development of B cells from immature CD34+CD38- cells was examined. Individual colonies, produced from clone-sorted CD34+CD38- cells by SCF, thrombopoietin and a complex of IL-6/soluble IL-6R with or without IL-3, were divided into two fractions and analysed for B-cell potential using co-culture on MS-5 with SCF and G-CSF, and haematopoietic potential using methylcellulose clonal culture. Although some colonies cultured without IL-3 showed both B-cell and haematopoietic potential, all the colonies cultured with IL-3 showed only haematopoietic potential. These results indicate that IL-3 has an inhibitory effect on the B-cell generation from human lymphohaematopoietic progenitor cells.
Miyamoto
K
K
Department of Clinical Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Tsuji
K
K
Maekawa
T
T
Asano
S
S
Nakahata
T
T
D000818:Animals; D018941:Antigens, CD19; D018952:Antigens, CD34; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D018920:Coculture Techniques; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism / Q000494:pharmacology*; D019891:Leukopoiesis / Q000187:drug effects*; D051379:Mice; D011485:Protein Binding; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology
D018941:Antigens, CD19; D018952:Antigens, CD34; D007377:Interleukin-3; D016185:Receptors, Interleukin-3; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor