S1P3 confers differential S1P-induced migration by autoreactive and non-autoreactive immature B cells and is required for normal B-cell development

Eur J Immunol. 2010 Mar;40(3):688-98. doi: 10.1002/eji.200939858.


During B-cell development, immature B-cell fate is determined by whether the BCR is engaged in the bone marrow. Immature B cells that are non-autoreactive continue maturation and emigrate from the marrow, whereas autoreactive immature B cells remain and are tolerized. However, the microenvironment where these events occur and the chemoattractants responsible for immature B-cell trafficking within and out of the bone marrow remain largely undefined. Sphingosine 1-phosphate (S1P) is a chemoattractant that directs lymphocyte trafficking and thymocyte egress and in this study we investigated whether S1P contributes to B-cell development, egress and positioning within the bone marrow. Our findings show that immature B cells are chemotactic toward S1P but that this response is dependent on Ag receptor specificity: non-autoreactive, but not autoreactive, immature B cells migrate toward S1P and are shown to require S1P3 receptor for this response. Despite this response, S1P3 is shown not to facilitate immature B-cell egress but is required for normal B-cell development including the positioning of transitional B cells within bone marrow sinusoids. These data indicate that S1P3 signaling directs immature B cells to a bone marrow microenvironment important for both tolerance induction and maturation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Differentiation / immunology*
  • Cell Separation
  • Chemotaxis, Leukocyte / immunology*
  • Flow Cytometry
  • Mice
  • Proprotein Convertases / immunology*
  • Proprotein Convertases / metabolism
  • Receptors, Lysosphingolipid / immunology*
  • Receptors, Lysosphingolipid / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Self Tolerance / immunology*
  • Serine Endopeptidases / immunology*
  • Serine Endopeptidases / metabolism
  • Sphingosine-1-Phosphate Receptors


  • Receptors, Lysosphingolipid
  • S1pr3 protein, mouse
  • Sphingosine-1-Phosphate Receptors
  • Proprotein Convertases
  • Serine Endopeptidases
  • membrane-bound transcription factor peptidase, site 1