C4b-Binding Protein (C4BP) Activates B Cells through the CD40 Receptor

Scott R. Brodeur, Federica Angelini, Leonard B. Bacharier, Anna M. Blom, Emiko Mizoguchi, Hiroshi Fujiwara, Alessandro Plebani, Luigi D. Notarangelo, Bjorn Dahlback, Erdyni Tsitsikov, Raif S. Geha

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

We demonstrate that the α 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 IKKγ/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.

Original languageEnglish
Pages (from-to)837-848
Number of pages12
JournalImmunity
Volume18
Issue number6
DOIs
StatePublished - Jun 1 2003

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