The growth response to IL-7 during normal human B cell ontogeny is restricted to B-lineage cells expressing CD34.
The growth of human B cell precursors can be supported by bone marrow (BM) stromal cells and IL-7, but the identity of the responding population is unknown. In the current study, we examined the growth characteristics of FACS-purified CD10+/CD34+/cytoplasmic mu- pro-B cells and CD10+/CD34-/cytoplasmic mu+ pre-B cells in an IL-7/BM stromal cell-dependent culture. Our results show that pro-B cells proliferate, whereas pre-B cells do not. Pro-B cell growth was dependent upon direct contact with BM stromal cells, because no growth occurred when pro-B cells were suspended in transwells above a BM stromal cell monolayer in the presence of IL-7. IL-7-stimulated pro-B cells partially differentiated into a pre-B cell population, on the basis of the loss of CD34 and terminal deoxynucleotidyl (TdT) expression, and the acquisition of cytoplasmic mu heavy chains. Examination of platelet endothelial cell adhesion molecule-1/CD31 expression on B cell precursors revealed a bimodal distribution: CD34+ pro-B cells exhibited a high density pattern and CD34- pre-B cells exhibited a low density pattern. The IL-7-induced differentiation of pro-B cells into pre-B cells included a shift from high CD31 to low CD31 expression. Interestingly, pro-B and pre-B cells expressed comparable levels of IL-7R, as determined by flow cytometry, even though pre-B cells were nonresponsive to IL-7 stimulation. Our collective results show that human pro-B cells require both IL-7 and direct contact with BM stromal cells to undergo proliferation and partial differentiation into the pre-B cell stage, whereas pre-B cells are nonresponsive to IL-7 and require other signals for their survival and growth.
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Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis 55455.
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D000328:Adult; D015703:Antigens, CD; D018952:Antigens, CD34; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D015415:Biomarkers; D001853:Bone Marrow / Q000196:embryology / Q000254:growth & development; D001854:Bone Marrow Cells; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D003238:Connective Tissue / Q000502:physiology; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D015260:Neprilysin
D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D016895:Culture Media, Serum-Free; D016207:Cytokines; D015851:Interleukin-7; D015260:Neprilysin