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Blood, 15 August 2004, Vol. 104, No. 4, pp. 933-941.
Prepublished online as a Blood First Edition Paper on May 4, 2004; DOI 10.1182/blood-2003-11-4013.
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Submitted December 9, 2003
Accepted April 13, 2004
Expression of the Chemokine Receptor CCR2 on Immature B Cells Negatively Regulates their Cytoskeletal Rearrangement and Migration
Liat Flaishon, Shirly Becker-Herman, Gili Hart, Yoram Levo, William A Kuziel, and Idit Shachar*
Immunology, Weizmann Institute of Science, Rehovot, Israel
Sourasky Medical Center, Tel-Aviv, Israel
Autoimmune and Inflammatory Diseases, Protein Design Labs, Inc., Fremont, CA, USA
* Corresponding author; email: idit.shachar{at}weizmann.ac.il.
Immature B cells are targeted to specific areas in the spleen, where a fraction of these cells receive signals that induce them to mature and participate in the immune response. In this study, we show that the C-C chemokine receptor 2 (CCR2) is transcribed in immature B cells, while its message is dramatically down regulated at the mature stage. CCR2 deficient cells exhibit upregulation of chemokine-induced actin polymerization, migration, and homing to the lymph nodes of immature B cells. In addition, we demonstrate that control of homing by CCR2 is mediated by its ligand, CCL2/JE, which is secreted by B cells and downregulates the SDF-1 signaling cascade. Thus, this study describes an additional, previously uncharacterized, role for CCR2 and its ligand as negative regulators of the homing of immature B cells.
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