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IL‐7 is required for B cell development from adult human bone marrow due to decreased B lymphoid generative capacity
Author(s) -
Milford TerryAnn,
Parrish Yasmin Khan,
Baez Ineavely,
Rogerio Jaqueline Willeman,
Sahakian Eva,
Kagoda Mercy,
Benitez Abigail,
Huang Grace,
Payne Kimberly J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.842.5
Subject(s) - cd19 , lymphopoiesis , haematopoiesis , bone marrow , b cell , stem cell , biology , microbiology and biotechnology , immunology , flow cytometry , chemistry , antibody
Human B lymphopoiesis is thought to differ from that in mouse with respect to the requirement for IL‐7. Here we investigated the role of IL‐7 in human B cell development using an in vitro model based on co‐culturing human hematopoietic stem cells (HSCs) on primary stroma from adult human bone marrow (BM). Addition of IL‐7 to this co‐culture model increased B cell production by ∼40‐fold. IL‐7‐induced increases were dose‐dependent and specific to CD19+ cells. Flow cytometry analysis of STAT5 phosphorylation, IL‐7Rα, and the proliferation antigen, ki‐67, indicate that IL‐7 acts directly on B cell precursors where it increases proliferation, but not cell survival. The effects of IL‐7 were most profound in cultures with adult BM HSCs where few, if any, human B lineage cells are generated in the absence of IL‐7 activity. When co‐cultures initiated with cord blood (CB) and BM HSCs were compared, IL‐7‐induced increases were similar in magnitude, and B cell precursors responded similarly to IL‐7. However, a comparison of the generative capacity of CB and BM HSCs showed that the ability of BM HSCs to give rise to CD19+, but not CD19− cells, was 40 times less than that of CB HSCs. Our results provide evidence that IL‐7 is critical for B cell production from HSCs in adult BM due to their low B lymphoid generative capacity as compared to HSCs in CB. Supported by NIH K01 DK066163 and the Dept. of Pathology and Human Anatomy and the Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine.