title: C4b-binding protein (C4BP) activates B cells through the CD40 receptor.
abstract: We demonstrate that the alpha chain of human C4b binding protein (C4BP) binds directly to CD40 on human B cells at a site that differs from that used by CD40 ligand. C4BP induces proliferation, upregulation of CD54 and CD86 expression, and IL4-dependent IgE isotype switching in normal B cells but not in B cells from patients with CD40 or IKKgamma/NEMO deficiencies. Furthermore, C4BP colocalized with B cells in the germinal centers of human tonsils. These observations suggest that C4BP is an activating ligand for CD40 and establish a novel interface between complement and B cell activation.
authors.affiliation: Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Brodeur
authors.forename: Federica
authors.initials: F
authors.lastname: Angelini
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Bacharier
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
authors.forename: Emiko
authors.initials: E
authors.lastname: Mizoguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Bjorn
authors.initials: B
authors.lastname: Dahlback
authors.forename: Erdyni
authors.initials: E
authors.lastname: Tsitsikov
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules; D002455:Cell Division / Q000502:physiology; D003169:Complement Inactivator Proteins / Q000378:metabolism*; D006023:Glycoproteins; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D014066:Palatine Tonsil / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D019013:CD40 Antigens; C069847:CD66 antigens; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007073:Immunoglobulin E; D048051:p38 Mitogen-Activated Protein Kinases