title: Covalently-bound human C4b dimers consisting of C4B isotype show higher hemolytic activity than those of C4A in the C3-bypass complement pathway.
abstract: The ability to form a covalent dimer of human C4b was investigated with purified isotypes C4A and C4B, and antibody-sensitized liposomes supplemented with C1. In this system, no C4A or C4B formed a complex with the antibody or C1. Whereas both C4A and C4B isotypes formed dimers to a similar extent, C4B formed an ester-linked dimer and C4A an amide-linked dimer. Both of these dimers served as a subunit for the C3-bypass pathway C5 convertase, since liposomes bearing Ab, C1 and a dimer of C4A or C4B, allowed the formation of C5 convertase by the addition of C2. The degree of complement-mediated liposome lysis however, was observed to be 2-3 times higher in the C4B-bearing particles than in those bearing C4A. These results indicate that the second C4b-binding site on the first C4b is different between C4A and C4B, and that in the C3-bypass pathway, C4B has a higher degree of hemolytic activity than C4A, as in the conventional classical complement pathway.
authors.affiliation: Department of Immunology, Center for Adult Diseases Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Masaki
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: I
authors.initials: I
authors.lastname: Nakanishi
authors.forename: H
authors.initials: H
authors.lastname: Kitamura
authors.forename: T
authors.initials: T
authors.lastname: Seya
mesh_terms: D001704:Biopolymers / Q000502:physiology; D003176:Complement C3 / Q000502:physiology; D050577:Complement C3-C5 Convertases / Q000096:biosynthesis*; D015934:Complement C4a / Q000378:metabolism / Q000502:physiology*; D015935:Complement C4b / Q000378:metabolism / Q000502:physiology*; D015941:Complement Hemolytic Activity Assay / Q000379:methods*; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008081:Liposomes
chemical_list: D001704:Biopolymers; D003176:Complement C3; D008081:Liposomes; D015934:Complement C4a; D015935:Complement C4b; D050577:Complement C3-C5 Convertases