First Author | Donovan EE | Year | 2010 |
Journal | Eur J Immunol | Volume | 40 |
Issue | 3 | Pages | 688-98 |
PubMed ID | 20039302 | Mgi Jnum | J:157770 |
Mgi Id | MGI:4436953 | Doi | 10.1002/eji.200939858 |
Citation | Donovan EE, et al. (2009) 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 40(3):688-698 |
abstractText | 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. |