TY - JOUR
T1 - C4b-Binding Protein (C4BP) Activates B Cells through the CD40 Receptor
AU - Brodeur, Scott R.
AU - Angelini, Federica
AU - Bacharier, Leonard B.
AU - Blom, Anna M.
AU - Mizoguchi, Emiko
AU - Fujiwara, Hiroshi
AU - Plebani, Alessandro
AU - Notarangelo, Luigi D.
AU - Dahlback, Bjorn
AU - Tsitsikov, Erdyni
AU - Geha, Raif S.
N1 - Funding Information:
We thank Dr. Jordan Orange, Dr. N. Ramesh, Haifa Jabara, and Dr. Vassilios Lougaris for patient samples, unpublished data, technical expertise, and critical comments. This work was supported by USPHS grants AI-31451 (R.S.G.) and T32 AI-07512 (S.R.B.) and by a kind gift from Mr. N. Wallace. A.M.B. and B.D. are supported by grants from the Swedish Research Council. A.P. was supported by EU grant QLG1-CT-2001-01536.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0038503986&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(03)00149-3
DO - 10.1016/S1074-7613(03)00149-3
M3 - Article
C2 - 12818164
AN - SCOPUS:0038503986
SN - 1074-7613
VL - 18
SP - 837
EP - 848
JO - Immunity
JF - Immunity
IS - 6
ER -