IL-3 Increases Production of B Lymphoid Progenitors from Human CD34+CD38- Cells

• Published in: The Journal of immunology (1950) 2000-09, Vol.165 (5), p.2382-2389
• Main Authors: Crooks, Gay M, Hao, Qian-Lin, Petersen, Denise, Barsky, Lora W, Bockstoce, David
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - physiology; ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Antigens, CD; Antigens, CD19 - biosynthesis; Antigens, CD34 - biosynthesis; Antigens, Differentiation - biosynthesis; B-Lymphocyte Subsets - cytology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; Cell Culture Techniques; Cell Differentiation - immunology; Cells, Cultured; Child; Child, Preschool; Drug Combinations; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; Humans; Interleukin-3 - physiology; Interleukin-7 - physiology; Ligands; Membrane Glycoproteins; Membrane Proteins - physiology; NAD+ Nucleosidase - biosynthesis; Stromal Cells - immunology; Time Factors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.5.2382

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.