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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3137-3144. Prepublished online as a Blood First Edition Paper on August 3, 2007; DOI 10.1182/blood-2007-02-073130. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: blood-2007-02-073130v1 111/6/3137    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Google Scholar Articles by Widhopf, G. F. Articles by Kipps, T. J. PubMed PubMed Citation Articles by Widhopf, G. F., II Articles by Kipps, T. J. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Nonstochastic pairing of immunoglobulin heavy and light chains expressed by chronic lymphocytic leukemia B cells is predicated on the heavy chain CDR3 George F. Widhopf, II1,2, Craig J. Goldberg1,3, Traci L. Toy1,3, Laura Z. Rassenti13, William G. Wierda1,4, John C. Byrd1,5, Michael J. Keating1,4, John G. Gribben1,6, Kanti R. Rai1,7, and Thomas J. Kipps13 1 Chronic Lymphocytic Leukemia Research Consortiuim, La Jolla, CA; 2 Division of Hematology/Oncology, Department of Medicine, and 3 Moores Cancer Center, University of California San Diego, La Jolla; 4 Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston; 5 Division of Hematology and Oncology, The Ohio State University, Columbus; 6 Cancer Research UK Medical Oncology Unit, Barts and The London School of Medicine, London, United Kingdom; and 7 Division of Hematology/Oncology, Long Island Jewish Medical Center, New Hyde Park, NY We analyzed the immunoglobulin (Ig) variable heavy (IGHV) and variable light chain genes used by leukemia cells of 258 unrelated patients with chronic lymphocytic leukemia (CLL) found to express unmutated Ig heavy chains (IgH) encoded by a 51p1 allele of IGHV1-69 among 1846 CLL patients examined. We found each had at least 98% homology to an identified germline IGKV or IGLV gene. Within the 258 IgH, we identified heavy chain CDR3 (HCDR3) motifs encoded by certain unmutated IGHD and IGHJ genes with restricted reading frames. Frequent and restricted use of particular IGKV and IGLV genes revealed nonstochastic pairing of disparate Ig light chains (IgL) with IgH that had restricted HCDR3 motifs designated CLL69A, -B, -C, and -D. Eighty-six percent (19/22) of CLL cases that expressed motif CLL69B encoded by IGHD2-2/IGHJ6 had distinctive IgL encoded by IGKV1-39. Similarly, 83% (5/6) of samples with motif CLL69D encoded by IGHD2-2/IGHJ6 expressed IGKV3-11, 100% (25/25) with motif CLL69A encoded by IGHD3-16/IGHJ3 used IGKV3-20, and 77% (10/13) with motif CLL69C encoded by IGHD3-3/IGHJ6 expressed IGLV3-9. This study reveals nonstochastic pairing of IgH with particular IgL that is predicated upon Ig HCDR3 structure, providing compelling evidence for selection of antibodies expressed in CLL by conventional antigens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. M. Ghia, S. Jain, G. F. Widhopf II, L. Z. Rassenti, M. J. Keating, W. G. Wierda, J. G. Gribben, J. R. Brown, K. R. Rai, J. C. Byrd, et al. Use of IGHV3-21 in chronic lymphocytic leukemia is associated with high-risk disease and reflects antigen-driven, post-germinal center leukemogenic selection Blood, May 15, 2008; 111(10): 5101 - 5108. [Abstract] [Full Text] [PDF] T. J. Kipps Chronic Lymphocytic Leukemia: Prognostic Markers and Revised Criteria for Treatment and Response Assessment ASCO Educational Book, January 1, 2008; 2008(1): 286 - 290. [Abstract] [Full Text] [PDF]

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