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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 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 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 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. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 Sundström, Ola Söderberg, Göran Roos, and Richard Rosenquist From the Departments of Genetics and Pathology and of Oncology, Radiology, and Clinical Immunology, Uppsala University, Uppsala, Sweden; the Department of Hematology, Linköping University Hospital, Linköping, Sweden; the Department of Biomedicine and Surgery, Linköping University, Linköping, Sweden; the Department of Hematology at Karolinska University Hospital, Huddinge, Sweden; the Department of Clinical Chemistry at Tampere University Hospital, Tampere, and Helsinki University Central Hospital (HUSLAB), Helsinki, Finland; and the Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. We recently identified a chronic lymphocytic leukemia (CLL) subgroup using the immunoglobulin variable heavy-chain (VH) gene VH3-21 with almost identical heavy-chain complementarity determining region 3s (HCDR3s) and preferential variable 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, diversity (D), and joining (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 6 of these 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 implies 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: M. Colombat, H. Mal, C. Copie-Bergman, J. Diebold, D. Damotte, P. Callard, M. Fournier, J.-P. Farcet, M. Stern, and M.-H. Delfau-Larue Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor Blood, September 1, 2008; 112(5): 2004 - 2012. [Abstract] [Full Text] [PDF] M. Muzio, B. Apollonio, C. Scielzo, M. 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