Complement Factor B is a protein crucial to the body’s immune defense system. It is a component of the alternative pathway of complement activation, a process that fights infections and clears damaged cells. This protein helps the body eliminate harmful substances.
Understanding the Complement System
The complement system is part of the innate immune system, serving as an early defense against pathogens and cellular debris. It consists of numerous plasma proteins that work together in a cascading series of reactions, identifying and eliminating foreign microorganisms and damaged host cells.
Its purpose includes enhancing the ability of antibodies and phagocytic cells to clear microbes, promoting inflammation, and directly attacking pathogen cell membranes. While part of the innate immune response, the complement system can also be activated by antibodies, linking it to the adaptive immune system. Its components, primarily synthesized in the liver, circulate in the blood as inactive precursors, ready for activation.
Complement Factor B’s Specific Role
Complement Factor B circulates in the blood as a single-chain polypeptide. Its activation within the complement system is specific to the alternative pathway.
This pathway initiates when Factor B binds to C3b, a fragment of complement component C3, in the presence of magnesium ions.
The binding of Factor B to C3b facilitates its cleavage by Factor D, a serine protease. This cleavage yields two fragments: the non-catalytic chain Ba and the catalytic subunit Bb. The Bb fragment remains associated with C3b, forming the alternative pathway C3 convertase, known as C3bBb.
The C3bBb complex is a key enzyme in the alternative pathway, responsible for cleaving more C3 into C3a and C3b. This process amplifies the complement response by generating additional C3b molecules, forming more C3 convertase complexes. The C3 convertase also forms the C5 convertase, which cleaves C5 into C5a and C5b.
The alternative pathway C5 convertase forms when an additional C3b molecule binds to the C3bBb complex, resulting in C3bBbC3b. This C5 convertase cleaves C5, generating C5a, a potent mediator of inflammation, and C5b, which initiates the assembly of the membrane attack complex (MAC) that lyses target cells.
Implications of Complement Factor B Dysregulation
Dysfunction of Complement Factor B, whether due to insufficient levels or excessive activity, can lead to various health issues.
A deficiency in Complement Factor B can increase susceptibility to bacterial infections. Individuals with such deficiencies are vulnerable to infections caused by Neisseria meningitidis, a bacterium known to cause meningitis and other severe conditions.
Conversely, overactivity or uncontrolled activation of the alternative pathway, in which Factor B is a central component, can contribute to autoimmune diseases and inflammatory conditions. For instance, mutations in the gene encoding Factor B have been linked to atypical hemolytic uremic syndrome (aHUS), a severe kidney disorder characterized by excessive complement activation on endothelial cell surfaces.
Overactive Factor B can also contribute to C3 glomerulopathy (C3G), rare kidney diseases where uncontrolled complement activation leads to complement protein deposition in the kidney’s filtering units. Dysregulation of the complement system, including Factor B, has also been implicated in the development and progression of age-related macular degeneration (AMD), a common cause of vision loss.