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Identification and characterization of circulating human transitional B cells

Murine B-cell development begins in bone marrow and results in the generation of immature transitional B cells that transit to the spleen to complete their maturation. It remains unclear whether the same developmental pathway takes place in humans. Using markers characteristic of human bone marrow i...

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Published in:Blood 2005-06, Vol.105 (11), p.4390-4398
Main Authors: Sims, Gary P., Ettinger, Rachel, Shirota, Yuko, Yarboro, Cheryl H., Illei, Gabor G., Lipsky, Peter E.
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Language:English
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container_issue 11
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creator Sims, Gary P.
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description Murine B-cell development begins in bone marrow and results in the generation of immature transitional B cells that transit to the spleen to complete their maturation. It remains unclear whether the same developmental pathway takes place in humans. Using markers characteristic of human bone marrow immature B cells, we have identified a population of circulating human B cells with a phenotype most similar to mouse transitional type I (T1) B cells, although these human counterparts express CD5. These cells die rapidly in culture, and B-cell activation factor member of the tumor necrosis factor (TNF) family (BAFF) does not effect their survival regardless of B-cell receptor (BCR) stimulation. In contrast, bone marrow stromal cells or interleukin-4 (IL-4) significantly enhanced their survival. In the presence of T-cell signals provided by IL-4 or CD40 ligation, BCR stimulation can induce progression into cell cycle. Interestingly, circulating B cells that phenotypically and functionally resemble murine T2 B cells are found in cord blood and adult peripheral blood, suggesting that B-cell maturation may not be restricted to the spleen. Notably, increased proportions of T1 B cells were found in blood of patients with systemic lupus erythematosus (SLE), although bone marrow production and selection appeared to be normal.
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Lipsky, Intramural Research Program Autoimmunity Branch Chief, National Institute of Arthritis and Musculoskeletal and Skin Diseases, 9000 Rockville Pike, Building 10, Room 6D47C, Bethesda, MD 20892-1860; e-mail: lipskyp@mail.nih.gov.</notes><notes>The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.</notes><notes>Prepublished online as Blood First Edition Paper, February 8, 2005; DOI 10.1182/blood-2004-11-4284.</notes><abstract>Murine B-cell development begins in bone marrow and results in the generation of immature transitional B cells that transit to the spleen to complete their maturation. It remains unclear whether the same developmental pathway takes place in humans. 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source ScienceDirect Journals
subjects B-Cell Activating Factor
B-Lymphocytes - cytology
Biological and medical sciences
Blood Cells
Bone Marrow Cells
Cell Cycle
Cell Survival
Coculture Techniques
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Immunobiology
Immunophenotyping
Interleukin-4 - pharmacology
Lupus Erythematosus, Systemic - blood
Lymphocyte Activation
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
Membrane Proteins - pharmacology
Stromal Cells
Tumor Necrosis Factor-alpha - pharmacology
title Identification and characterization of circulating human transitional B cells
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