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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3647-3654. Prepublished online as a Blood First Edition Paper on June 10, 2004; DOI 10.1182/blood-2004-01-0346. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2004-01-0346v1 104/12/3647    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 Weller, S. Articles by Weill, J.-C. Search for Related Content PubMed PubMed Citation Articles by Weller, S. Articles by Weill, J.-C. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire Sandra Weller, Moritz C. Braun, Bruce K. Tan, Andreas Rosenwald, Corinne Cordier, Mary Ellen Conley, Alessandro Plebani, Dinakhanta S. Kumararatne, Damien Bonnet, Olivier Tournilhac, Gil Tchernia, Birte Steiniger, Louis M. Staudt, Jean-Laurent Casanova, Claude-Agnès Reynaud, and Jean-Claude Weill From the Institut National de la Santé et de la Recherche Médicale (INSERM) U373; INSERM IFR 94, Service commun de Tri Cellulaire; Service de Cardiologie Pédiatrique; Unité d'Hématologie et d'Immunologie Pédiatrique; and INSERM U550, Faculté de Médecine Necker-Enfants Malades and Hôpital Necker, Paris, France; Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Immunology, St Jude Children's Research Hospital, University of Tennessee College of Medicine, Memphis; Departments of Pediatrics, University of Brescia and Istituto di Medicina Molecolare "Angelo Nocivelli," Spedali Civili, Brescia, Italy; Departments of Clinical Immunology and Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom; Fédération des Maladies Infectieuses, CHU Hôtel Dieu, Clermont-Ferrand, France; Laboratoire d'Hématologie, Hopital de Bicêtre,Assistance Publique des Hopitaux de Paris, Kremlin-Bicêtre, France; and the Institute of Anatomy and Cell Biology, University of Marburg, Germany. The human peripheral B-cell compartment displays a large population of immunoglobulin M–positive, immunoglobulin D–positive CD27+ (IgM+IgD+CD27+) "memory" B cells carrying a mutated immunoglobulin receptor. By means of phenotypic analysis, complementarity-determining region 3 (CDR3) spectratyping during a T-independent response, and gene-expression profiling of the different blood and splenic B-cell subsets, we show here that blood IgM+IgD+CD27+ cells correspond to circulating splenic marginal zone B cells. Furthermore, analysis of this peripheral subset in healthy children younger than 2 years shows that these B cells develop and mutate their immunoglobulin receptor during ontogeny, prior to their differentiation into T-independent antigen-responsive cells. It is therefore proposed that these IgM+IgD+CD27+ B cells provide the splenic marginal zone with a diversified and protective preimmune repertoire in charge of the responses against encapsulated bacteria. 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