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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2879-2885. Prepublished online as a Blood First Edition Paper on June 24, 2004; DOI 10.1182/blood-2004-01-0132. This Article Full Text (PDF) All Versions of this Article: 2004-01-0132v1 104/9/2879    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 Tobin, G. Articles by Rosenquist, R. Search for Related Content PubMed PubMed Citation Articles by Tobin, G. Articles by Rosenquist, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 13, 2004 Accepted June 7, 2004 Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia Gerard Tobin, Ulf Thunberg, Karin Karlsson, Fiona Murray, Anna Laurell, Kerstin Willander, Gunilla Enblad, Mats Merup, Juhani Vilpo, Gunnar Juliusson, Christer Sundstrom, Ola Soderberg, Goran Roos, and Richard Rosenquist* Dept. of Genetics and Pathology, Uppsala University, Uppsala, Sweden Dept. of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden Dept. of Hematology, Linkoping University Hospital, Linkoping, Sweden Dept. of Biomedicine and Surgery, Linkoping University, Linkoping, Sweden Dept. of Medicine, Huddinge University Hospital, Stockholm, Sweden Dept. of Clinical Chemistry, Tampere University Hospital and Helsinki University Central Hospital (HUSLAB), Tampere, Finland Dept. of Medical Biosciences, Pathology, Umea University, Umea, Sweden * Corresponding author; email: richard.rosenquist{at}genpat.uu.se. We recently identified a chronic lymphocytic leukemia (CLL) subgroup utilizing the immunoglobulin VH3-21 gene with almost identical heavy chain complementarity determining region 3:s (HCDR3s) and preferential light chain VL gene usage, suggesting recognition of a common antigen epitope in this subset. To further explore the B-cell receptors (BCRs) in CLL, we characterized 407 VH rearrangements amplified from 346 CLLs regarding VH/D/JH gene usage and performed multiple alignment of the HCDR3 sequences. These analyses revealed 3 small subsets (2 VH1-69 groups, 7 cases, and 1 VH1-2 group, 5 cases) with highly restricted HCDR3 features including identical VH/D/JH usage, HCDR3 lengths and shared N-sequences, in addition to the VH3-21 group (22 cases). Furthermore, another 3 groups (9 VH1-3+ cases, 3 VH1-18+ cases and 5 VH4-39+ cases) had essentially identical VH/D/JH use and similar HCDR3 lengths but less conserved N-regions. Analysis in all these six subgroups showed restriction in VL gene use, whereas no association between VH and VL usage was found in cases without HCDR3 similarities. Altogether, structurally similar HCDR3s associated with preferential VL gene usage imply selection of BCRs, especially in subsets showing high HCDR3 similarities, thus pointing to restricted antigen recognition sites and possibly involvement of specific antigens in CLL development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L.-A. Sutton, E. Kostareli, A. Hadzidimitriou, N. Darzentas, A. Tsaftaris, A. Anagnostopoulos, R. Rosenquist, and K. Stamatopoulos Extensive intraclonal diversification in a subgroup of chronic lymphocytic leukemia patients with stereotyped IGHV4-34 receptors: implications for ongoing interactions with antigen Blood, November 12, 2009; 114(20): 4460 - 4468. [Abstract] [Full Text] [PDF] T. Seiler, M. Woelfle, S. 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