Interleukin 7 independent development of human B cells.
Mammalian hematopoietic stem cell (HSC) commitment and differentiation into lymphoid lineage cells proceed through a series of developmentally restricted progenitor compartments. A complete understanding of this process, and how it differs from HSC commitment and differentiation into cells of the myeloid/erythroid lineages, requires the development of model systems that support HSC commitment to the lymphoid lineages. We now describe a human bone marrow stromal cell culture that preferentially supports commitment and differentiation of human HSC to CD19+ B-lineage cells. Fluorescence activated cell sorterpurified CD34++/lineage-cells were isolated from fetal bone marrow and cultured on human fetal bone marrow stromal cells in serum-free conditions containing no exogenous cytokines. Over a period of 3 weeks, CD34++/lineage- cells underwent commitment, differentiation, and expansion into the B lineage. Progressive changes included: loss of CD34, acquisition of and graded increases in the level of cell surface CD19, and appearance of immature B cells expressing mu/kappa or mu/lambda cell surface Ig receptors. The tempo and phenotype of B-cell development was not influenced by the addition of IL-7 (10 ng/ml), or by the addition of goat anti-IL-7 neutralizing antibody. These results indicate a profound difference between mouse and human in the requirement for IL-7 in normal B-cell development, and provide an experimental system to identify and characterize human bone marrow stromal cell-derived molecules crucial for human B lymphopoiesis.
Prieyl
J A
JA
Department of Laboratory Medicine/Pathology, University of Minnesota Cancer Center, Minneapolis, USA.
LeBien
T W
TW
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D001853:Bone Marrow / Q000196:embryology / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005333:Fetus; D005434:Flow Cytometry; D006041:Goats; D006410:Hematopoiesis / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000494:pharmacology*; D007700:Kinetics; D008322:Mammals; D051379:Mice; D011971:Receptors, Immunologic / Q000096:biosynthesis; D013045:Species Specificity; D017154:Stromal Cells; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D015851:Interleukin-7; D011971:Receptors, Immunologic