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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, CD / biosynthesis
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Antigens, CD / genetics
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Antigens, Differentiation / biosynthesis
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Antigens, Differentiation / genetics
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B-Lymphocytes / metabolism*
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CD40 Antigens / metabolism*
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Carrier Proteins / metabolism
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Cell Adhesion Molecules
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Cell Division / physiology
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Complement Inactivator Proteins / metabolism*
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Glycoproteins*
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Humans
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Immunoglobulin E / biosynthesis
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Intercellular Adhesion Molecule-1 / biosynthesis
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Intercellular Adhesion Molecule-1 / genetics
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Interleukin-4 / metabolism
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NF-kappa B / metabolism
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Palatine Tonsil / metabolism
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Up-Regulation
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p38 Mitogen-Activated Protein Kinases
Substances
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Antigens, CD
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Antigens, Differentiation
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CD40 Antigens
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CD66 antigens
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Carrier Proteins
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Cell Adhesion Molecules
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Complement Inactivator Proteins
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Glycoproteins
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NF-kappa B
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Intercellular Adhesion Molecule-1
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Interleukin-4
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Immunoglobulin E
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p38 Mitogen-Activated Protein Kinases