title: Human bone marrow stromal cells simultaneously support B and T/NK lineage development from human haematopoietic progenitors: a principal role for flt3 ligand in lymphopoiesis.
abstract: The regulation of human early lymphopoiesis remains unclear. B- and T-lineage cells cannot develop simultaneously with conventional stromal cultures. Here we show that telomerized human bone marrow stromal cells supported simultaneous generation of CD19(+) CD34(lo/-) CD10(+) cyCD79a(+) CD20(+/-) VpreB(-)  pro-B cells and CD7(+) CD34(+)  CD45RA(+) CD56(-) cyCD3(-)  early T/Natural Killer (NK) cell precursors from human haematopoietic progenitors, and the generation of both lymphoid precursors was promoted by flt3 ligand (flt3L). On the other hand, stem cell factor or thrombopoietin had little or no effect when used alone. However, both acted synergistically with flt3L to augment the generation of both lymphoid precursors. Characteristics of these lymphoid precursors were evaluated by gene expression profiles, rearrangements of IgH genes, or replating assays. Similar findings were observed with primary human bone marrow stromal cells. Notably, these two lymphoid-lineage precursors were generated without direct contact with stromal cells, indicating that early B and T/NK development can occur, at least in part, by stromal cell-derived humoral factors. In serum-free cultures, flt3L elicited similar effects and appeared particularly important for B cell development. The findings of this study identified the potential of human bone marrow stromal cells to support human early B and T lymphopoiesis and a principal role for flt3L during early lymphopoiesis.
authors.affiliation: Haematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nakamori
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Kohshi
authors.initials: K
authors.lastname: Ohishi
authors.forename: Kei
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuko
authors.initials: K
authors.lastname: Ino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Masuya
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D038041:Lymphopoiesis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D008565:Membrane Proteins; C084881:flt3 ligand protein