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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2134-2142. Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-11-4024. This Article Full Text (PDF) All Versions of this Article: 2003-11-4024v1 104/7/2134    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 Kriangkum, J. Articles by Pilarski, L. M Search for Related Content PubMed PubMed Citation Articles by Kriangkum, J. Articles by Pilarski, L. M Social Bookmarking                   What's this? Submitted November 25, 2003 Accepted January 16, 2004 Clonotypic IgH VDJ sequence analysis in Waldenstrom's macroglobulinemia suggests an unusual B cell origin and expansion of polyclonal B cells in peripheral blood Jitra Kriangkum, Brian J Taylor, Steven P Treon, Michael J Mant, Andrew R Belch, and Linda M Pilarski* Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada Hematologic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Medicine, University of Alberta, Edmonton, AB, Canada * Corresponding author; email: lpilarsk{at}ualberta.ca. Analysis of clonotypic IgM from 15 patients with Waldenstrom's macroglobulinemia (WM) showed a strong preferential usage of VH3/JH4 gene families. Identification of the WM IgM-VDJ was validated by single cell analysis, confirming of its presence in most B cells. Despite the extensive hypermutated VH genes in 13/15 patients, statistical analysis of FR/CDR mutation patterns suggests that they may have escaped antigenic selection. Neither intraclonal diversity nor isotype switching were detectable. Both membrane and secreted forms of clonotypic IgM transcripts were present in bone marrow and blood. Single cell analysis showed that clonotypic B cells coexpress CD20, sIgM and sIgD but lack CD138. Most B cells lacked memory marker CD27 despite their hypermutated variable regions otherwise suggestive of memory status. At diagnosis, circulating B cells in WM are largely clonotypic. However, when monoclonal IgM levels are decreased, clonotypic frequencies were substantially reduced despite elevated CD20+ cells, shown to be polyclonal by DNA sequencing and CDR3 fragment analysis. Thus, WM includes expansion of circulating, polyclonal B cells. Overall, this work suggests that WM may originate from a largely VH3-restricted, somatically mutated, predominantly CD27-IgM+IgD+ population that cannot undergo class switching, suggestive of B cells that may have bypassed the germinal center. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. W. Ho, E. Hatjiharissi, B. T. Ciccarelli, A. R. Branagan, Z. R. Hunter, X. Leleu, O. Tournilhac, L. Xu, K. O'Connor, R. J. Manning, et al. CD27-CD70 interactions in the pathogenesis of Waldenstrom macroglobulinemia Blood, December 1, 2008; 112(12): 4683 - 4689. [Abstract] [Full Text] [PDF] S. Berentsen Rituximab for the treatment of autoimmune cytopenias Haematologica, December 1, 2007; 92(12): 1589 - 1596. [Full Text] [PDF] A. Vijay and M. A. Gertz Waldenstrom macroglobulinemia Blood, June 15, 2007; 109(12): 5096 - 5103. [Abstract] [Full Text] [PDF] C. Wei, J. Anolik, A. Cappione, B. Zheng, A. Pugh-Bernard, J. 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