Complement C4B (Chido/Rodgers blood group) | Elisa - Clia - Antibody - Protein

Background

Complement component 4B (C4B) is an essential protein in the classical and lectin pathways of the complement system, a key component of the innate immune system. It is encoded by the C4B gene located in the major histocompatibility complex (MHC) class III region on chromosome 6. This region is highly polymorphic and is involved in immune response regulation. The C4B protein is part of the complement system, which enhances the ability of antibodies and phagocytic cells to clear pathogens and damaged cells, promote inflammation, and attack the pathogen's cell membrane.

Protein Structure

• Domain Composition: The C4B protein is a glycoprotein composed of 1,745 amino acids and has a molecular weight of approximately 200 kDa. It is initially synthesized as a single polypeptide chain that is subsequently cleaved into three chains: α, β, and γ.
• Functional Domains:
• α Chain: Contains a critical site for cleavage by the enzyme C1s, resulting in the formation of C4b and the small peptide C4a.
• Thioester Bond: A highly reactive site that allows C4b to covalently bind to pathogen surfaces, which is crucial for its function in opsonization and forming part of the C3 and C5 convertase complexes.
• Chido/Rodgers Blood Group Antigens: These antigens are important for blood transfusion compatibility and are encoded within the C4B protein.

Classification and Subtypes

• C4A and C4B: C4B is one of two isoforms of complement component 4, the other being C4A. Although they share high sequence similarity, they differ in certain amino acid residues that result in functional differences; C4B has a preference for binding hydroxyl groups, while C4A prefers amino groups.
• Polymorphisms: The C4B gene exhibits extensive polymorphism, which contributes to the variability in immune responses among individuals. These polymorphisms can affect the expression levels and functional efficacy of the C4B protein.

Function and Biological Significance

• Complement Activation: C4B is activated by cleavage into C4b by the protease C1s, a step that is critical in the classical and lectin pathways of the complement system. C4b then binds covalently to microbial surfaces or immune complexes.
• Opsonization: The covalent attachment of C4b to pathogen surfaces tags them for recognition and ingestion by phagocytic cells, facilitating the clearance of pathogens.
• Formation of Convertases: C4b binds to C2a to form the C3 convertase (C4b2a), which is essential for the activation of C3 and subsequent steps leading to the formation of the membrane attack complex (MAC).

Clinical Issues

• Deficiencies and Autoimmunity: Deficiencies in C4B are associated with an increased risk of autoimmune diseases, such as systemic lupus erythematosus (SLE) and recurrent infections due to impaired complement activation.
• Transfusion Compatibility: Polymorphisms in C4B, including those defining the Chido/Rodgers blood group antigens, are significant in the context of blood transfusions and transplant compatibility.
• Disease Susceptibility: Variations in the C4B gene have been linked to susceptibility to various autoimmune conditions and infections, impacting the overall effectiveness of the immune response.

Summary

Complement C4B is a vital component of the immune system, playing crucial roles in pathogen recognition, opsonization, and the activation of downstream complement components. Its function and efficiency are influenced by genetic polymorphisms, which can affect individual susceptibility to autoimmune diseases and infections. Understanding the structure, function, and clinical significance of C4B is essential for developing targeted therapies for immune-related disorders and ensuring compatibility in transfusion and transplantation medicine.