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

Area of Science:

• Immunology
• Complement System
• B cell Biology

Background:

• CD40 is a critical receptor on B cells involved in immune responses.
• The complement system plays a role in adaptive immunity.
• The interaction between complement proteins and B cell surface receptors is not fully understood.

Purpose of the Study:

• To investigate the interaction between C4b-binding protein (C4BP) and CD40 on human B cells.
• To determine the functional consequences of C4BP binding to CD40.
• To explore the role of C4BP in B cell activation and germinal center reactions.

Main Methods:

• Surface plasmon resonance to assess C4BP binding to CD40.
• Flow cytometry to analyze B cell proliferation and marker expression (CD54, CD86).
• Cytokine measurements (IL-4) and IgE isotype switching assays.
• Immunohistochemistry to visualize C4BP and B cell colocalization in human tonsil tissues.

Main Results:

• The alpha chain of C4BP directly binds to CD40 on human B cells at a distinct site from the CD40 ligand.
• C4BP induces B cell proliferation, upregulates CD54 and CD86 expression, and promotes IL-4-dependent IgE isotype switching.
• These effects are dependent on functional CD40 and IKKgamma/NEMO signaling pathways.
• C4BP was observed to colocalize with B cells within the germinal centers of human tonsils.

Conclusions:

• C4BP acts as a novel activating ligand for CD40 on human B cells.
• This finding establishes a previously unrecognized interface between the complement system and B cell activation.
• C4BP may play a significant role in regulating B cell responses within lymphoid tissues.