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Sims, G. P. et al. Identification and characterization of circulating human transitional B cells. Blood 105, 4390-4398

Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, MD, USA.
Blood (Impact Factor: 10.43). 07/2005; 105(11):4390-8. DOI: 10.1182/blood-2004-11-4284
Source: PubMed

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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    • "Consistently, our data allow us to exclude that the expansion of transitional B cells is due to homeostatic proliferation since we demonstrated the absence of replication history in this subset. Transitional B cells are found expanded in immunodeficient conditions [40] or autoimmune diseases [41] and represent a reservoir of autoreactive B cells [42]. The cohort of patients analyzed here did not show any overt sign of autoimmunity, probably due to their young age. "
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    • "However, it was recently reported that a fraction of human peripheral blood (PB) B cells are transitional, but not mature B cells, and that these cells are CD5 + (Sims et al., 2005). Importantly, at birth the majority of CD5 + B cells are transitional B cells (Ha et al., 2008; Marie-Cardine et al., 2008; Sims et al., 2005). Hence, in the previous GEP study, mostly transitional B cells and not mature CD5 + B cells were compared with CLL. "
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    Journal of Experimental Medicine 11/2012; 209(12):2183-2198. DOI:10.1084/jem.20120833 · 13.91 Impact Factor
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    • "Early efforts to identify human B1 cells using CD5 expression combined with expression of a B cell specific antigen, as in the murine system, have not been revealing because CD5 is expressed on multiple human B cell populations including activated, pre-naïve, and transitional B cells (Freedman et al., 1989; Sims et al., 2005; Lee et al., 2009a; Griffin et al., 2011a). "
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