Cutting Edge: Acute and chronic exposure of immature B cells to antigen leads to impaired homing and SHIP1-dependent reduction in stromal cell-derived factor-1 responsiveness |
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Authors: | Brauweiler Anne Merrell Kevin Gauld Stephen B Cambier John C |
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Institution: | Integrated Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, CO 80206, USA. |
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Abstract: | An encounter of B cells with cognate self Ags in the periphery can lead to anergy, a condition characterized by altered anatomical localization, shortened life span, and refractility to Ag stimulation. We recently reported that an immature B cell encounter with cognate self-Ag in the bone marrow can also lead to anergy. In this study we show that anergic as well as acutely Ag-stimulated immature B cells are defective in stromal cell-derived factor-1 (SDF-1)-induced calcium mobilization and migration and do not localize to bone marrow following adoptive transfer. This hyporesponsiveness does not involve CXCR4 modulation. However, BCR signal-mediated hyporesponsiveness to SDF-1 is associated with phosphorylation of the 5-inositol phosphatase SHIP1 and requires SHIP1 expression. Therefore, an encounter with cognate Ag may, by preventing SDF-1-induced phosphatidylinositol 3,4,5-triphosphate accumulation, trigger premature emigration of immature B cells from bone marrow. |
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