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Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-10-3123. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3123v1 101/11/4464    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 Craxton, A. Articles by Clark, E. A. Search for Related Content PubMed PubMed Citation Articles by Craxton, A. Articles by Clark, E. A. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4464-4471 IMMUNOBIOLOGY Macrophage- and dendritic cell—dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF Andrew Craxton, Dario Magaletti, Elizabeth J. Ryan, and Edward A. Clark From the Department of Microbiology, University of Washington, Seattle; Department of Immunology, University of Washington, Seattle; and the Regional Primate Research Center, University of Washington, Seattle. Macrophages and dendritic cells play an important role in regulating B-cell responses, including proliferation to antigens such as trinitrophenyl (TNP)—Ficoll and TNP-Brucella abortus. However, the mechanisms and molecule(s) that regulate these processes are relatively undefined. In this report, we show that human macrophages generated in vitro strongly costimulate proliferation of dense human tonsillar B cells ligated via their B-cell antigen receptor (BCR) but not proliferation via CD40. Similarly, dendritic cells also markedly enhance BCR-activated B-cell proliferation. Soluble molecule(s) are required for human macrophages to costimulate proliferation of B cells triggered via their BCR. Importantly, a TACI (trans-membrane activator and CAML interactor)—Fc fusion protein inhibits both macrophage- and dendritic cell (DC)—dependent BCR-activated B-cell proliferation, indicating a requirement for at least one of the known TACI ligands, BAFF and/or APRIL. Consistent with a major role for BAFF, macrophages release BAFF at levels sufficient to potently costimulate BCR-induced B-cell proliferation. In addition, BAFF is more than 100-fold more potent than APRIL in enhancing BCR-mediated human B-cell proliferation. Furthermore, immunodepletion of APRIL under conditions that prevent APRIL-mediated B-cell costimulation does not block macrophage enhancement of B-cell proliferation. Finally, there is no correlation between the high levels of a proliferation-inducing ligand (APRIL) expressed by macrophages compared with DCs and the similar abilities of macrophages and DCs to enhance BCR-stimulated B-cell proliferation. In summary, our results suggest that macrophage- and DC-derived B-cell—activating factor belonging to the TNF family (BAFF) represents a key molecule by which macrophages and DCs directly regulate human B-cell proliferative responses to T-cell—independent stimuli. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. S. Kim, J.-Y. Park, I. Jou, and S. M. Park Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia J. Leukoc. Biol., August 1, 2009; 86(2): 349 - 359. 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