This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jahrsdorfer, B. Articles by Hartmann, G. Search for Related Content PubMed PubMed Citation Articles by Jahrsdorfer, B. Articles by Hartmann, G.

B-Cell Lymphomas Differ in their Responsiveness to CpG Oligodeoxynucleotides

¹ Division of Clinical Pharmacology and ² Department of Internal Medicine, Division of Hematology, and ³ Department of Otorhinolaryngology, University of Munich, Munich, Germany; ⁴ Institute of Immunology, University of Heidelberg, Heidelberg, Germany; and ⁵ Holden Comprehensive Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa

Requests for reprints: Gunther Hartmann, Klinische Pharmakologie, Medizinische Klinik Innenstadt, Ludwig-Maximilians-Universitat München, Ziemssenstrasse 1, 80336, Munich, Germany. Phone: 49-89-5160-2331; Fax: 49-89-5160-4406; E-mail: ghartmann{at}lrz.uni-muenchen.de.

Human B cells detect CpG motifs within microbial DNA via TLR9. Synthetic CpG oligodeoxynucleotides are currently being tested in clinical trials for the therapy of different types of B cell non-Hodgkin's lymphoma. However, there is only limited information on the CpG oligodeoxynucleotide sensitivity of primary malignant B cells of different non-Hodgkin's lymphoma entities. Here we found that most B-cell malignancies except plasmacytoma respond to CpG oligodeoxynucleotides by up-regulating expression of costimulatory and antigen-presenting molecules, by increasing expression of CD20, and by proliferation. In an in vitro analysis of 41 individual patient-derived primary tumor samples, B-cell chronic lymphocytic leukemia (B-CLL) and marginal zone lymphoma showed the strongest activation upon stimulation with CpG oligodeoxynucleotides. Small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, and large cell lymphoma showed an intermediate response. Consistent with CpG oligodeoxynucleotides sensitivity, TLR9 mRNA was present in B-CLL but absent in plasmacytoma. Although CpG oligodeoxynucleotides induced proliferation in all CpG oligodeoxynucleotide–sensitive types of B-cell malignancies, proliferation was weaker than in normal B cells and at least for B-CLL was followed by increased apoptosis. In conclusion, B-cell malignancies show significant differences in their responsiveness to CpG oligodeoxynucleotides. Focusing clinical studies on patients with highly CpG oligodeoxynucleotide–sensitive B-cell malignancies may improve the clinical outcome of such trials.

Key Words: Toll-like receptor • B-cell malignancy • B-cell activation • non-Hodgkin's lymphoma

This article has been cited by other articles:

				P. Knuefermann, M. Schwederski, M. Velten, P. Krings, H. Ehrentraut, M. Rudiger, O. Boehm, K. Fink, U. Dreiner, C. Grohe, et al. Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of Toll-like receptor 9 Cardiovasc Res, April 1, 2008; 78(1): 26 - 35. [Abstract] [Full Text] [PDF]

				C. Grandjenette, A. Kennel, G. C. Faure, M. C. Bene, and P. Feugier Expression of functional toll-like receptors by B-chronic lymphocytic leukemia cells Haematologica, September 1, 2007; 92(9): 1279 - 1281. [Abstract] [Full Text] [PDF]

				M. A. Taubman, X. Han, K. B. LaRosa, S. S. Socransky, and D. J. Smith Periodontal Bacterial DNA Suppresses the Immune Response to Mutans Streptococcal Glucosyltransferase Infect. Immun., August 1, 2007; 75(8): 4088 - 4096. [Abstract] [Full Text] [PDF]

				B. Jahrsdorfer, S. E. Blackwell, J. E. Wooldridge, J. Huang, M. W. Andreski, L. S. Jacobus, C. M. Taylor, and G. J. Weiner B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation Blood, October 15, 2006; 108(8): 2712 - 2719. [Abstract] [Full Text] [PDF]

				M. Hoogendoorn, J. Olde Wolbers, W. M. Smit, M. R. Schaafsma, I. Jedema, R. M.Y. Barge, R. Willemze, and J.H. F. Falkenburg Primary Allogeneic T-Cell Responses against Mantle Cell Lymphoma Antigen-Presenting Cells for Adoptive Immunotherapy after Stem Cell Transplantation Clin. Cancer Res., July 15, 2005; 11(14): 5310 - 5318. [Abstract] [Full Text] [PDF]