Complement component 4B (C4B)

Complement component 4B (**C4B**) is one isoform encoded by one locus within the human major histocompatibility complex; it differs from its close paralog *complement component 4A* (*C4A*) by only four amino acids but has distinct immunological properties. Upon activation via classical or lectin pathway triggers—such as antibody-antigen complexes—native ~200 kDa precursor protein is cleaved into two fragments: - **C4a**, a small peptide (~9 kDa) acting as an anaphylatoxin mediating local inflammation, - **C4b**, a large fragment (~190 kDa) that covalently attaches to pathogen surfaces via an exposed thioester bond. Surface-bound **C4b acts both as an opsonin marking targets for phagocytosis and forms part of the proteolytically active enzyme complex ("classical pathway" C3 convertase, i.e., *C４ｂ２ａ*) that amplifies downstream immune responses through further cleavage events. Regulation occurs primarily through interaction with proteins like factor I cofactor *c４ｂ-binding protein*, which degrades surface-bound c４ｂ preventing excessive host tissue damage. Dysregulation—either deficiency or overactivity—is implicated in autoimmune conditions, heightened infection risk, chronic inflammation, and certain neurodegenerative diseases such as Alzheimer's disease where aberrant synaptic pruning occurs due partly to inappropriate complement activity.[1][2][3]

Other names

Complement C4BChido/Rodgers blood group (refers to antigenic determinants on the protein)C4b (refers to the activated fragment after cleavage)

Potential mechanisms include: - Inhibition/blockade of proteolytic cleavage or function to prevent formation/activation of downstream convertases - Neutralization by monoclonal antibodies or small molecules that bind active sites or regulatory regions These approaches aim to reduce inappropriate immune activation and tissue damage mediated by uncontrolled complement activity[2].