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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Bibliographic Details
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.
Format: Article
Language:English
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
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2004-11-4284