Identification and characterization of circulating human transitional B cells

Blood. 2005 Jun 1;105(11):4390-8. doi: 10.1182/blood-2004-11-4284. Epub 2005 Feb 8.

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.

MeSH terms

  • B-Cell Activating Factor
  • B-Lymphocytes / cytology*
  • Blood Cells*
  • Bone Marrow Cells
  • Cell Cycle
  • Cell Survival
  • Coculture Techniques
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Interleukin-4 / pharmacology
  • Lupus Erythematosus, Systemic / blood
  • Lymphocyte Activation
  • Membrane Proteins / pharmacology
  • Stromal Cells
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • B-Cell Activating Factor
  • Membrane Proteins
  • TNFSF13B protein, human
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor-alpha
  • Interleukin-4