C4b-binding protein (C4BP) activates B cells through the CD40 receptor

Immunity. 2003 Jun;18(6):837-48. doi: 10.1016/s1074-7613(03)00149-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / genetics
  • B-Lymphocytes / metabolism*
  • CD40 Antigens / metabolism*
  • Carrier Proteins / metabolism
  • Cell Adhesion Molecules
  • Cell Division / physiology
  • Complement Inactivator Proteins / metabolism*
  • Glycoproteins*
  • Humans
  • Immunoglobulin E / biosynthesis
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Intercellular Adhesion Molecule-1 / genetics
  • Interleukin-4 / metabolism
  • NF-kappa B / metabolism
  • Palatine Tonsil / metabolism
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • CD40 Antigens
  • CD66 antigens
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Complement Inactivator Proteins
  • Glycoproteins
  • NF-kappa B
  • Intercellular Adhesion Molecule-1
  • Interleukin-4
  • Immunoglobulin E
  • p38 Mitogen-Activated Protein Kinases