title: Identification and characterization of circulating human transitional B cells.
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.
authors.affiliation: Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, MD, USA.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Sims
authors.forename: Rachel
authors.initials: R
authors.lastname: Ettinger
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shirota
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Yarboro
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Illei
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000166:cytology*; D001773:Blood Cells; D001854:Bone Marrow Cells; D002453:Cell Cycle; D002470:Cell Survival; D018920:Coculture Techniques; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000494:pharmacology; D017154:Stromal Cells; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D053264:B-Cell Activating Factor; D008565:Membrane Proteins; C505719:TNFSF13B protein, human; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4