Identification and characterization of circulating human transitional B cells

GP Sims, R Ettinger, Y Shirota, CH Yarboro, GG Illei… - Blood, 2005 - ashpublications.org
GP Sims, R Ettinger, Y Shirota, CH Yarboro, GG Illei, PE Lipsky
Blood, 2005ashpublications.org
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 …
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. 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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