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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4390-4398.
Prepublished online as a Blood First Edition Paper on February 8, 2005; DOI 10.1182/blood-2004-11-4284.


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IMMUNOBIOLOGY

Identification and characterization of circulating human transitional B cells

Gary P. Sims, Rachel Ettinger, Yuko Shirota, Cheryl H. Yarboro, Gabor G. Illei, and Peter E. Lipsky

From the Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD

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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