Q.43 Factor H, a complement regulatory protein in plasma, binds C3b and
(A) competes with factor B to displace Bb from convertase.
(B) initiates the catabolism of C3b into inactivate products.
(C) then binds to C3bBb convertase.
(D) acts as a cofactor for factor I.

Factor H acts as a cofactor for factor I when bound to C3b.​

The correct answer to this CSIR NET Life Sciences question is (D) acts as a cofactor for factor I. Factor H, a key plasma regulator of the alternative complement pathway, binds C3b and enables its proteolytic inactivation.​

Option Analysis

(A) competes with factor B to displace Bb from convertase.
Factor H binds C3b and competes with factor B for C3b binding sites to prevent C3bB formation, but it primarily displaces Bb from the preformed C3bBb convertase through decay-accelerating activity rather than direct competition for displacement. This option inaccurately emphasizes competition over decay acceleration.​

(B) initiates the catabolism of C3b into inactive products.
Factor H does not directly initiate C3b breakdown; it serves as a cofactor that requires factor I to cleave C3b into iC3b and further inactive fragments like C3c and C3dg. Without factor I, no catabolism occurs.​

(C) then binds to C3bBb convertase.
While Factor H does bind the C3bBb convertase to accelerate Bb dissociation, the phrasing “then binds to C3bBb convertase” implies a sequential step after C3b binding without specifying its regulatory role, making it less precise than the cofactor function.​

(D) acts as a cofactor for factor I.
This is correct. Factor H binds C3b via its N-terminal SCR1-4 domains and acts as a cofactor for factor I-mediated cleavage of C3b to iC3b, preventing excessive complement amplification on host cells.​

Factor H binds C3b and acts as a cofactor for Factor I, serving as a primary regulator in the alternative complement pathway to protect host cells from immune damage. This 150-kDa glycoprotein, produced mainly by the liver, maintains plasma levels around 1-2 µM and exerts three key functions: competing with Factor B for C3b, accelerating decay of C3bBb convertase, and enabling Factor I to inactivate C3b.​

Key Regulatory Mechanisms

• C3b Binding and Competition: Factor H’s N-terminal domains (SCR1-4) bind C3b, blocking Factor B attachment and preventing C3 convertase assembly.​

• Decay Acceleration: It displaces Bb from C3bBb, destabilizing the convertase.​

• Cofactor Activity: Bound Factor H recruits Factor I to cleave C3b into iC3b, halting amplification; C-terminal SCR19-20 enhance surface recognition via sialic acid and GAGs.​

Clinical Relevance

Dysfunctional Factor H links to diseases like atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD) due to unchecked complement activation. Pathogens like bacteria exploit Factor H binding for immune evasion.​

This mechanism is critical for CSIR NET aspirants studying complement control in molecular immunology.​