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Inhibitory effect of interleukin 3 on early development of human B‐lymphopoiesis
Author(s) -
Miyamoto Koichiro,
Tsuji Kohichiro,
Maekawa Taira,
Asano Shigetaka,
Nakahata Tatsutoshi
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02956.x
Subject(s) - stem cell factor , lymphopoiesis , cd38 , interleukin 3 , stem cell , haematopoiesis , cd19 , biology , cd34 , b cell , stromal cell , clone (java method) , interleukin 15 , cell culture , interleukin 5 , microbiology and biotechnology , immunology , interleukin , cytokine , il 2 receptor , t cell , cancer research , flow cytometry , antibody , immune system , biochemistry , dna , genetics
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 α‐chain (IL‐3Rα) + cells, but not IL‐3Rα − cells, produced B cells, and IL‐3 suppressed the B‐cell generation from CD34 + IL‐3Rα + cells, suggesting that IL‐3 exerts an inhibitory effect through the binding to IL‐3Rα 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.