HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brauweiler, A. Articles by Cambier, J. C. Search for Related Content PubMed PubMed Citation Articles by Brauweiler, A. Articles by Cambier, J. C. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

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 Responsiveness¹

Integrated Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, CO 80206

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant DK047121-11. J.C.C. is an Ida and Cecil Green endowed Professor of Cell Biology.

² Address correspondence and reprint requests to Dr. John C. Cambier, Department of Immunology, National Jewish Medical and Research Center, 1400 Jackson Street, Denver CO 80206. E-mail address: cambierj{at}njc.org

³ Abbreviations used in this paper: SDF-1, stromal cell-derived factor-1; HEL, hen egg lysozyme; mIg, membrane Ig; PIP₃, phosphatidylinositol 3,4,5-trisphosphate;

This article has been cited by other articles:

				J. E. Crowley, J. E. Stadanlick, J. C. Cambier, and M. P. Cancro Fc{gamma}RIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation Blood, February 12, 2009; 113(7): 1464 - 1473. [Abstract] [Full Text] [PDF]