IL-3 increases production of B lymphoid progenitors from human CD34+CD38- cells.
The effect of IL-3 on the B lymphoid potential of human hemopoietic stem cells is controversial. Murine studies suggest that B cell differentiation from uncommitted progenitors is completely prevented after short-term exposure to IL-3. We studied B lymphopoiesis after IL-3 stimulation of uncommitted human CD34+CD38- cells, using the stromal cell line S17 to assay the B lymphoid potential of stimulated cells. In contrast to the murine studies, production of CD19+ B cells from human CD34+CD38- cells was significantly increased by a 3-day exposure to IL-3 (p < 0.001). IL-3, however, did not increase B lymphopoiesis from more mature progenitors (CD34+CD38+ cells) or from committed CD34-CD19+ B cells. B cell production was increased whether CD34+CD38- cells were stimulated with IL-3 during cocultivation on S17 stroma, on fibronectin, or in suspension. IL-3Ralpha expression was studied in CD34+ populations by RT-PCR and FACS. High IL-3Ralpha protein expression was largely restricted to myeloid progenitors. CD34+CD38- cells had low to undetectable levels of IL-3Ralpha by FACS. IL-3-responsive B lymphopoiesis was specifically found in CD34+ cells with low or undetectable IL-3Ralpha protein expression. IL-3 acted directly on progenitor cells; single cell analysis showed that short-term exposure of CD34+CD38- cells to IL-3 increased the subsequent cloning efficiency of B lymphoid and B lymphomyeloid progenitors. We conclude that short-term exposure to IL-3 significantly increases human B cell production by inducing proliferation and/or maintaining the survival of primitive human progenitors with B lymphoid potential.
Crooks
G M
GM
Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA. gcrooks@chla.usc.edu
Hao
Q L
QL
Petersen
D
D
Barsky
L W
LW
Bockstoce
D
D
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000276:Adjuvants, Immunologic / Q000502:physiology; D015703:Antigens, CD; D018941:Antigens, CD19 / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis*; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000502:physiology; D009244:NAD+ Nucleosidase / Q000096:biosynthesis*; D017154:Stromal Cells / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018941:Antigens, CD19; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D004338:Drug Combinations; D007377:Interleukin-3; D015851:Interleukin-7; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C084881:flt3 ligand protein; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1