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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Available from: Gary Sims, Mar 13, 2014
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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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    Journal of Autoimmunity 12/2013; 50(100). DOI:10.1016/j.jaut.2013.10.006 · 7.02 Impact Factor
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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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    ABSTRACT: The cellular origin of chronic lymphocytic leukemia (CLL) is still debated, although this information is critical to understanding its pathogenesis. Transcriptome analyses of CLL and the main normal B cell subsets from human blood and spleen revealed that immunoglobulin variable region (IgV) gene unmutated CLL derives from unmutated mature CD5+ B cells and mutated CLL derives from a distinct, previously unrecognized CD5+CD27+ post–germinal center B cell subset. Stereotyped V gene rearrangements are enriched among CD5+ B cells, providing independent evidence for a CD5+ B cell derivation of CLL. Notably, these CD5+ B cell populations include oligoclonal expansions already found in young healthy adults, putatively representing an early phase in CLL development before the CLL precursor lesion monoclonal B cell lymphocytosis. Finally, we identified deregulated proteins, including EBF1 and KLF transcription factors, that were not detected in previous comparisons of CLL and conventional B cells.
    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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    ABSTRACT: Controversy over the frequency of human B1 cells in normal individuals has arisen as different labs have begun to employ non-uniform techniques to study this population. The phenotypic profile and relative paucity of circulating human B1 cells place constraints on methodology to identify and isolate this population. Multiple steps must be optimized to insure accurate enumeration and optimal purification. In the course of working with human B1 cells we have developed a successful strategy that provides consistent analysis of B1 cells for frequency determination and efficient isolation of B1 cells for functional studies. Here we discuss issues attendant to identifying human B1 cells and outline a carefully optimized approach that leads to uniform and reproducible data.
    Frontiers in Immunology 05/2012; 3:122. DOI:10.3389/fimmu.2012.00122
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