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.
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.
Brauweiler
Anne
A
Integrated Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, CO 80206, USA.
Merrell
Kevin
K
Gauld
Stephen B
SB
Cambier
John C
JC
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D020013:Calcium Signaling / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology; D000072181:Inositol Polyphosphate 5-Phosphatases; D051379:Mice; D008822:Mice, Transgenic; D018129:Phosphatidylinositol Phosphates / Q000276:immunology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D019718:Receptors, CXCR4 / Q000276:immunology
D000941:Antigens; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D018129:Phosphatidylinositol Phosphates; D011947:Receptors, Antigen, B-Cell; D019718:Receptors, CXCR4; C060974:phosphatidylinositol 3,4,5-triphosphate; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases