A functional VCBP-C1q interaction in amphioxus reveals evolutionary origins of the classical complement pathway

Area of Science:

• Immunology
• Evolutionary Biology
• Biochemistry

Background:

• The evolutionary origins of the classical complement pathway, a key immune defense, are not fully understood.
• The interplay between immunoglobulin (Ig) and C1q is crucial but complex in complement system evolution.

Purpose of the Study:

• To investigate the role of Ig superfamily members in primitive complement activation.
• To explore the functional relationship between VCBP5 and C1q in the basal chordate amphioxus.

Main Methods:

• Identified and characterized variable region-containing chitin-binding protein 5 (VCBP5) in amphioxus.
• Assessed VCBP5 expression, binding affinity to E. coli, and its effect on bactericidal activity.
• Investigated the interaction between recombinant VCBP5 (rVCBP5) and BjC1q, and the subsequent recruitment of BjMASP1/3.

Main Results:

• VCBP5 expression increased upon E. coli stimulation and localized to specific tissues.
• rVCBP5 bound E. coli and enhanced humoral bactericidal activity, protecting against bacterial proliferation in vivo.
• VCBP5 directly interacted with BjC1q, facilitating the recruitment of BjMASP1/3 to trigger complement activation.

Conclusions:

• A functional partnership between VCBP5 and C1q was identified in amphioxus, indicating a primitive complement activation pathway.
• This discovery sheds light on the evolutionary emergence of the classical complement pathway from its early components.