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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3316-3325. Prepublished online as a Blood First Edition Paper on July 25, 2007; DOI 10.1182/blood-2007-05-089409. This Article Full Text (PDF) All Versions of this Article: blood-2007-05-089409v1 110/9/3316    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 Burkle, A. Articles by Burger, J. A. Search for Related Content PubMed PubMed Citation Articles by Burkle, A. Articles by Burger, J. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 8, 2007 Accepted July 19, 2007 Overexpression of the CXCR5 chemokine receptor, and its ligand, CXCL13 in B cell chronic lymphocytic leukemia Andrea Burkle, Matthias Niedermeier, Annette Schmitt-Graff, William G. Wierda, Michael J. Keating, and Jan A. Burger* Department of Medicine, Division of Hematology/Oncology, Freiburg University Hospital, Freiburg, Germany Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States Department of Pathology, Freiburg University Hospital, Freiburg, Germany * Corresponding author; email: jaburger{at}mdanderson.org. CXCL13 is a homeostatic chemokine for lymphocyte homing and positioning within follicles of secondary lymphoid tissues, acting through its cognate receptor, CXCR5. Moreover, the CXCR5-CXCL13 axis plays a unique role in trafficking and homing of B1 cells. Here, we report that chronic lymphocytic leukemia (CLL) B cells express high levels of functional CXCR5. CXCR5 expression levels were similar on CLL B cells and normal, CD5+ B cells, and higher when compared to normal, CD5 negative B cells, TFH cells, or neoplastic B cells from other B cell neoplasias. Stimulation of CLL cells with CXCL13 induces actin polymerization, CXCR5 endocytosis, chemotaxis, and prolonged activation of p44/42 mitogen-activated protein kinases. Anti-CXCR5 antibodies, pertussis toxin, and wortmannin inhibited chemotaxis to CXCL13, demonstrating the importance of Gi proteins and PI3-kinases for CXCR5 signaling, respectively. Moreover, CLL patients had significantly higher CXCL13 serum levels than volunteers, and CXCL13 levels correlated with 2 microglobulin. We detected CXCL13 mRNA expression by nurselike cells, and high levels of CXCL13 protein in supernatants of CLL nurselike cell cultures. By immunohistochemistry, we detected CXCL13+-expression by CD68+ macrophages in situ within CLL lymph nodes. These data suggest that CXCR5 plays a role in CLL cell positioning and cognate interactions between CLL and CXCL13-secreting CD68+ accessory cells in lymphoid tissues. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. D Festa, K. Hankiewicz, S. Kim, J. Skurnick, L. J Wolansky, S. D Cook, and D. Cadavid Serum levels of CXCL13 are elevated in active multiple sclerosis Multiple Sclerosis, November 1, 2009; 15(11): 1271 - 1279. [Abstract] [PDF] J. A. Burger, P. Ghia, A. Rosenwald, and F. Caligaris-Cappio The microenvironment in mature B-cell malignancies: a target for new treatment strategies Blood, October 15, 2009; 114(16): 3367 - 3375. [Abstract] [Full Text] [PDF] L. Fischer, A. Korfel, S. Pfeiffer, P. Kiewe, H.-D. Volk, H. Cakiroglu, T. Widmann, and E. Thiel CXCL13 and CXCL12 in Central Nervous System Lymphoma Patients Clin. Cancer Res., October 1, 2009; 15(19): 5968 - 5973. [Abstract] [Full Text] [PDF] M. P. Quiroga, K. Balakrishnan, A. V. Kurtova, M. Sivina, M. J. Keating, W. G. Wierda, V. Gandhi, and J. A. Burger B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406 Blood, July 30, 2009; 114(5): 1029 - 1037. [Abstract] [Full Text] [PDF] S. Deaglio and F. Malavasi Chronic lymphocytic leukemia microenvironment: shifting the balance from apoptosis to proliferation Haematologica, June 1, 2009; 94(6): 752 - 756. [Full Text] [PDF] A. V. Kurtova, A. T. Tamayo, R. J. Ford, and J. A. Burger Mantle cell lymphoma cells express high levels of CXCR4, CXCR5, and VLA-4 (CD49d): importance for interactions with the stromal microenvironment and specific targeting Blood, May 7, 2009; 113(19): 4604 - 4613. [Abstract] [Full Text] [PDF] L.-Y. Feng, Z.-L. Ou, F.-Y. Wu, Z.-Z. Shen, and Z.-M. Shao Involvement of a Novel Chemokine Decoy Receptor CCX-CKR in Breast Cancer Growth, Metastasis and Patient Survival Clin. Cancer Res., May 1, 2009; 15(9): 2962 - 2970. [Abstract] [Full Text] [PDF] J. A. Burger, M. P. Quiroga, E. Hartmann, A. Burkle, W. G. Wierda, M. J. Keating, and A. Rosenwald High-level expression of the T-cell chemokines CCL3 and CCL4 by chronic lymphocytic leukemia B cells in nurselike cell cocultures and after BCR stimulation Blood, March 26, 2009; 113(13): 3050 - 3058. [Abstract] [Full Text] [PDF]

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