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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-01-0248. This Article Full Text (PDF) All Versions of this Article: 2002-01-0248v1 100/7/2321    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Honczarenko, M. Articles by Silberstein, L. E Search for Related Content PubMed PubMed Citation Articles by Honczarenko, M. Articles by Silberstein, L. E Social Bookmarking                   What's this? Submitted January 30, 2002 Accepted May 17, 2002 CCR5 binding chemokines modulate CXCL12 (SDF-1) induced responses of progenitor B cells in human bone marrow through heterologous desensitization of the CXCR4 chemokine receptor Marek Honczarenko, Yi Le, Aleksandra M Glodek, Marcin Majka, James J Campbell, Mariusz Z Ratajczak, and Leslie E Silberstein* Joint Program in Transfusion Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA * Corresponding author; email: leslie.silberstein{at}tch.harvard.edu. While the SDF-1 (CXCL12)/CXCR4 axis is important for B cell development, it is not yet clear to what extent CC chemokines might influence B lymphopoiesis. In the current study, we characterized CC chemokine receptor 5 (CCR5) expression and function of primary progenitor B cell populations in human bone marrow. CCR5 was expressed on all bone marrow B cells at levels between 150-200 molecules per cell. Stimulation of bone marrow B cells with the CCR5 binding chemokine MIP-1ß(CCL4) did not cause chemotaxis, but CCL4 was able to trigger potent calcium mobilization responses and activation of the mitogen activated protein kinase (MAPK) pathway in developing B cells. We also determined that CCR5 binding chemokines MIP-1(CCL3), CCL4 and RANTES (CCL5) specifically by signaling through CCR5, could affect all progenitor B cell populations through a novel mechanism involving heterologous desensitization of CXCR4. This cross-desensitization of CXCR4 was manifested by the inhibition of CXCL12 induced calcium mobilization, MAPK activation as well as chemotaxis. These findings indicate that CCR5 can indeed mediate biological responses of bone marrow B cells, even though these cell populations express low levels of CCR5 on their cell surface. Thus, by modulation of CXCR4 function, signaling through CCR5 may influence B lymphopoiesis by affecting the migration and maturation of B cell progenitors in the bone marrow microenvironment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Basu and H. E. Broxmeyer CCR5 Ligands Modulate CXCL12-Induced Chemotaxis, Adhesion, and Akt Phosphorylation of Human Cord Blood CD34+ Cells J. Immunol., December 1, 2009; 183(11): 7478 - 7488. [Abstract] [Full Text] [PDF] C. Vanpouille, A. Biancotto, A. Lisco, and B. Brichacek Interactions between Human Immunodeficiency Virus Type 1 and Vaccinia Virus in Human Lymphoid Tissue Ex Vivo J. Virol., November 15, 2007; 81(22): 12458 - 12464. [Abstract] [Full Text] [PDF] M. B. Rookmaaker, M. C. Verhaar, H. C. de Boer, R. Goldschmeding, J. A. Joles, H. A. Koomans, H.-J. Grone, and T. J. 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