Inhibitory effect of interleukin 3 on early development of human B‐lymphopoiesis

Abstract

Summary. 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 1 CD19 1 B cells were generated in the co-culture of cord blood CD34 1 cells, the addition of IL-3 to the co-culture suppressed the B-cell generation in a dose-dependent manner. In the co-culture, CD341 IL-3 receptor a-chain (IL-3Ra) 1 cells, but not IL3Ra 2 cells, produced B cells, and IL-3 suppressed the B-cell generation from CD341 IL-3Ra 1 cells, suggesting that IL-3 exerts an inhibitory effect through the binding to IL-3Ra on CD34 1 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 CD341 cells, before the generation of CD19 1 B cells, the effect of IL-3 on the early development of B cells from immature CD341 CD38 2 cells was examined. Individual colonies, produced from clone-sorted CD34 1 CD38 2 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.

Interleukin‐3 Promotes Proliferation and Differentiation of Human Hematopoietic Stem Cells but Reduces Their Repopulation Potential in NOD/SCID Mice

“…However, when looked at in context of the human HLA‐I + cells that were formed in the mice, a nonsignificant decrease of CD19 + B‐lymphoid cells was found following the transplantation of CB‐MNCs and was even less pronounced when CD34 + cells were used for transplantation. Again, this is in agreement with in vitro studies that show that IL‐3 exerts an inhibitory effect on the early developmental stages of B lymphopoiesis in mice and humans [14, 15, 27]. In one study, a bifunctional influence of IL‐3 has been shown in the mouse system.…”

“…Results of recent studies on the influence of IL‐3 are controversial. While it is widely accepted that IL‐3 supports the expansion of CD34 + cells and leads to high expansion rates of post‐progenitor and mature cells in vitro, as well as a reduced formation of B‐lymphoid cells [14, 15], it is still discussed whether the repopulating potential of IL‐3‐treated CD34 + cells is reduced [16, 17]. All studies to date have been based on a stem cell manipulation using human IL‐3 in vitro prior to transplantation [18].…”

Cytokine profiles of cord and adult blood leukocytes: differences in expression are due to differences in expression and activation of transcription factors

“…Surface receptor stimulation remained ineffective, whereas the presence of mitogens efficiently induced this cytokine. Although neither a precise mechanism nor a physiological influence of IL-3 on early hematopoietic processes is known, several lines of evidence suggest that IL-3 inhibits T and B lymphopoietic events and therefore should lead to reduced appearance of GvHD [ 18 ]. This hypothesis conflicts with our finding of reduced IL-3 production in CBL.…”

Human Basophils Modulate Plasma Cell Differentiation and Maturation

“…IL-3 is a hematopoietic factor in the bone marrow (39), and affects all cells residing here, including B cells in different stages of development ranging from transitional B cells to PC. Interestingly, IL-3 inhibits human B-lymphopoiesis in the bone marrow (40), whereas the survival of PC in the bone marrow is enhanced by IL-3-controlled expression of a proliferation-inducing ligand (APRIL) (41). Whether IL-3 had a direct effect on (developing) PC was not investigated in the cited study.…”