title: Complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) cooperate in the binding of hydrolyzed complement factor 3 (C3i) to human B lymphocytes.
abstract: The C3b-binding receptor, CR1/CD35, supports CR2/CD21-mediated activation of complement by human B lymphocytes, possibly by associating with CR2 to promote or stabilize the binding of hydrolyzed C3 (C3i), the primary component of the AP convertase, C3i-Bb. To evaluate this hypothesis, we examined the uptake kinetics and binding equilibria for C3i dimer interaction with human blood cells in the absence and presence of CR1- and CR2-blocking mAb. C3i displayed dual uptake kinetics to B lymphocytes, comprising of rapid binding to CR1 and slower binding to CR2. The forward rate constants (k(1)) for CR1 and CR2, operating independently, differed ca. 9-fold (k(1)=193+/-9.4 and 22.2+/-6.0 x 10(3) M(-1)s(-1), respectively). Equilibrium binding of C3i to B lymphocytes was also complex, varying in strength by ca. 13-fold over the C3i concentration range examined. The maximum association constant (K(a, max)=109+/-27.2 x 10(7) l/mole) was ca. 9- and 6-fold greater, respectively, than those for CR1 or CR2 acting alone (K(a)=13.2+/-5.3 and 18.5+/-3.5 x 10(7) l/mole). The high avidity of the CR1-CR2 complex for C3i is consistent with its rates of C3i uptake and release being determined by CR1 and CR2, respectively.
authors.affiliation: Institute of Medical Biology, University of Southern Denmark, Odense, Denmark. gleslie@health.sdu.dk
authors.forename: Robert Graham Quinton
authors.initials: RG
authors.lastname: Leslie
authors.forename: Wolfgang Maria
authors.initials: WM
authors.lastname: Prodinger
authors.forename: Claus Henrik
authors.initials: CH
authors.lastname: Nielsen
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism; D017463:Receptors, Complement 3b / Q000502:physiology*; D017464:Receptors, Complement 3d / Q000502:physiology*
chemical_list: D003176:Complement C3; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d