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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2755-2764. Prepublished online as a Blood First Edition Paper on January 7, 2008; DOI 10.1182/blood-2007-09-110858. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-09-110858v1 111/5/2755    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 Belnoue, E. Articles by Siegrist, C.-A. Search for Related Content PubMed PubMed Citation Articles by Belnoue, E. Articles by Siegrist, C.-A. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells Elodie Belnoue1, Maria Pihlgren1, Tracy L. McGaha1, Chantal Tougne1, Anne-Françoise Rochat1, Claudia Bossen2, Pascal Schneider2, Bertrand Huard3, Paul-Henri Lambert1, and Claire-Anne Siegrist1 1 World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, Departments of Pathology-Immunology and Pediatrics, University of Geneva, Geneva; 2 Department of Biochemistry, University of Lausanne, Epalinges; and 3 Louis Jeantet Laboratory, Departments of Dermatology and Pathology-Immunology, University Medical Center and Hospital, Geneva, Switzerland The persistence of serum IgG antibodies elicited in human infants is much shorter than when such responses are elicited later in life. The reasons for this rapid waning of antigen-specific antibodies elicited in infancy are yet unknown. We have recently shown that adoptively transferred tetanus toxoid (TT)–specific plasmablasts (PBs) efficiently reach the bone marrow (BM) of infant mice. However, TT-specific PBs fail to persist in the early-life BM, suggesting that they fail to receive the molecular signals that support their survival/differentiation. Using a proliferation-inducing ligand (APRIL)– and B-cell activating factor (BAFF) B-lymphocyte stimulator (BLyS)–deficient mice, we demonstrate here that APRIL is a critical factor for the establishment of the adult BM reservoir of anti-TT IgG-secreting cells. Through in vitro analyses of PB/plasma cell (PC) survival/differentiation, we show that APRIL induces the expression of Bcl-XL by a preferential binding to heparan sulfate proteoglycans at the surface of CD138+ cells. Last, we identify BM-resident macrophages as the main cells that provide survival signals to PBs and show that this function is slowly acquired in early life, in parallel to a progressive acquisition of APRIL expression. Altogether, this identifies APRIL as a critical signal for PB survival that is poorly expressed in the early-life BM compartment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Belnoue, T. Matthes, C.-A. Siegrist, and B. Huard Comment on "Dendritic Cells and Monocyte/Macrophages That Create the IL-6/APRIL-Rich Lymph Node Microenvironment Where Plasmablasts Mature" J. Immunol., May 1, 2009; 182(9): 5159 - 5159. [Full Text] [PDF] F. C. Kimberley, L. van Bostelen, K. Cameron, G. Hardenberg, J. A. Marquart, M. Hahne, and J. P. Medema The proteoglycan (heparan sulfate proteoglycan) binding domain of APRIL serves as a platform for ligand multimerization and cross-linking FASEB J, May 1, 2009; 23(5): 1584 - 1595. [Abstract] [Full Text] [PDF] E. Mohr, K. Serre, R. A. Manz, A. F. Cunningham, M. Khan, D. L. Hardie, R. Bird, and I. C. M. MacLennan Dendritic Cells and Monocyte/Macrophages That Create the IL-6/APRIL-Rich Lymph Node Microenvironments Where Plasmablasts Mature J. Immunol., February 15, 2009; 182(4): 2113 - 2123. [Abstract] [Full Text] [PDF]

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