Complement factor B

Complement factor B

Diagram of the alternative pathway of complement activation, showing the role of complement factor B.

Complement factor B is a crucial component of the complement system, which is part of the innate immune system. It plays a significant role in the alternative pathway of complement activation, which is one of the three pathways that activate the complement system, the others being the classical pathway and the lectin pathway.

Structure

Complement factor B is a single-chain glycoprotein that circulates in the blood plasma. It is synthesized primarily in the liver and consists of several domains, including a von Willebrand factor type A domain, a serine protease domain, and a complement control protein domain. These domains are essential for its function in the complement cascade.

Function

In the alternative pathway, complement factor B binds to C3b, a fragment of the complement component C3, forming a complex known as C3bB. This complex is then cleaved by the enzyme factor D to form C3bBb, which is a potent C3 convertase. The C3 convertase amplifies the complement response by cleaving additional C3 molecules into C3a and C3b, leading to a cascade of events that result in the opsonization of pathogens, recruitment of inflammatory cells, and formation of the membrane attack complex.

Regulation

The activity of complement factor B is tightly regulated to prevent damage to host tissues. Regulatory proteins such as factor H and decay-accelerating factor (DAF) help to control the activity of the C3 convertase by promoting the dissociation of C3bBb and facilitating the degradation of C3b.

Clinical significance

Dysregulation of complement factor B can lead to various diseases. Overactivation of the alternative pathway is implicated in conditions such as atypical hemolytic uremic syndrome (aHUS), age-related macular degeneration (AMD), and paroxysmal nocturnal hemoglobinuria (PNH). Conversely, deficiencies in factor B can result in increased susceptibility to infections due to impaired complement activation.

Related pages

• Complement system
• Alternative pathway
• Factor D
• Factor H
• Membrane attack complex