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B Lymphocyte Stimulator Regulates Adaptive Immune Responses by Directly Promoting Dendritic Cell Maturation¹

Department of Immunology, College of Medicine, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905

B lymphocyte stimulator (BLyS) is a well-known direct costimulator of adaptive immune cells, particularly B lineage cells. However, we have reported recently that BLyS is also able to activate monocytes. Other innate immune cells, such as dendritic cells (DCs), play a key role in the initiation of adaptive immune responses and the purpose of the current study was to assess whether there is a direct role for BLyS in modulating human DC functions. In this study, we show that BLyS induces DC activation and maturation. Thus, BLyS strongly induced up-regulation of surface costimulatory molecule expression and secretion of specific cytokines and chemokines in DCs. BLyS-stimulated DCs (BLyS-DCs) were also able to augment allogeneic CD4 T cell proliferation to a greater extent than control DCs. BLyS-DCs secreted elevated levels of the major Th1-polarizing cytokine, IL-12p70, and they promoted naive CD4 T cell differentiation into Th1 T cells. Regarding BLyS receptor expression, DCs primarily express cytoplasmic transmembrane activator and CAML interactor; however, low levels of cell surface transmembrane activator and CAML interactor are expressed as well. Collectively, our data suggest that BLyS may modulate adaptive immune cells indirectly by inducing DC maturation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants CA105258 and CA062242 (awarded to D.F.J.).

² Address correspondence and reprint requests to Dr. Diane F. Jelinek, Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Guggenheim 4, Rochester, MN 55905. E-mail address: jelinek.diane{at}mayo.edu

³ Abbreviations used in this paper: DC, dendritic cell; BLyS, B lymphocyte stimulator; BCMA, B cell maturation Ag; TACI, transmembrane activator and CAML interactor; SS, Sjogren’s syndrome; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; MNC, mononuclear cell; rh, recombinant human; PB, polymyxin b; CBA, cytometric bead array; RT, room temperature; GRO, growth-related oncogene; FDC, follicular DC.