Generation of peripheral B cells occurs via two spatially and temporally distinct pathways

Blood. 2007 Mar 15;109(6):2521-8. doi: 10.1182/blood-2006-04-018085. Epub 2006 Nov 14.

Abstract

We have identified a population of newly formed bone marrow (BM) B cells that shares multiple characteristics with late transitional B cells in the spleen. Both late splenic transitional B cells and cells within this uncharacterized BM population expressed the cell-surface phenotype AA4(+) CD23(+), yet the developmental kinetics and the renewal rate of AA4(+) CD23(+) BM B cells mirrored recently formed BM B cells. Further, unlike the least mature B cells in the BM and spleen, AA4(+) CD23(+) BM B cells expressed the homing receptor CD62L, were dependent on the antiapoptotic cytokine receptor BR3 and the tec family kinase Btk, and proliferated in response to IL-4 plus CD40 stimulation. Finally, frequencies of lambda light chain-positive B cells declined among AA4(+) CD23(+) B cells in both the BM and spleen, suggesting that V-gene selection events correlate with CD23 expression in both compartments. These observations indicate that the first step in B-cell maturation occurs in both the BM and the periphery and suggest that recently formed B cells exit the BM as a heterogeneous pool of immature and semimature B cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • B-Cell Activating Factor / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Bone Marrow / immunology
  • CD40 Antigens / metabolism
  • Cell Differentiation
  • Cell Survival
  • Cells, Cultured
  • Gene Expression Regulation
  • Interleukin-4 / metabolism
  • Kinetics
  • L-Selectin / genetics
  • L-Selectin / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mutation / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Complement / metabolism
  • Receptors, IgE / metabolism
  • Spleen / metabolism

Substances

  • B-Cell Activating Factor
  • CD40 Antigens
  • Membrane Glycoproteins
  • Receptors, Complement
  • Receptors, IgE
  • complement 1q receptor
  • L-Selectin
  • Interleukin-4
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase