title: Plasmacytoid dendritic cells regulate autoreactive B cell activation via soluble factors and in a cell-to-cell contact manner.
abstract: Plasmacytoid dendritic cells (pDCs) are specialized type I IFN producers, which play an important role in pathogenesis of autoimmune disorders. Dysregulated autoreactive B cell activation is a hallmark in most autoimmune diseases. This study was undertaken to investigate interactions between pDCs and autoreactive B cells. After coculture of autoreactive B cells that recognize self-Ag small nuclear ribonucleoprotein particles with activated pDCs, we found that pDCs significantly enhance autoreactive B cell proliferation, autoantibody production, and survival in response to TLR and BCR stimulation. Neutralization of IFN-alpha/beta and IL-6 abrogated partially pDC-mediated enhancement of autoreactive B cell activation. Transwell studies demonstrated that pDCs could provide activation signals to autoreactive B cells via a cell-to-cell contact manner. The involvement of the ICAM-1-LFA-1 pathway was revealed as contributing to this effect. This in vitro enhancement effect was further demonstrated by an in vivo B cell adoptive transfer experiment, which showed that autoreactive B cell proliferation and activation were significantly decreased in MyD88-deficient mice compared with wild-type mice. These data suggest the dynamic interplay between pDCs and B cells is required for full activation of autoreactive B cells upon TLR or BCR stimulation.
authors.affiliation: Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Chuanlin
authors.initials: C
authors.lastname: Ding
authors.forename: Yihua
authors.initials: Y
authors.lastname: Cai
authors.forename: Jose
authors.initials: J
authors.lastname: Marroquin
authors.forename: Suzanne T
authors.initials: ST
authors.lastname: Ildstad
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D016169:Lymphocyte Function-Associated Antigen-1; D017411:Ribonucleoproteins, Small Nuclear; D018799:Intercellular Adhesion Molecule-1