Modulation of the alternative complement pathways by beta 1 H globulin.

TLDR

The binding mechanisms of C3b and inhibition of alternative pathway convertases C3bB and C3bBP remain unknown. A‑C3bINA, a C3b inactivator accelerator, was isolated from human plasma. Beta 1 H, a carbohydrate‑rich, asymmetric polypeptide contaminant of C3 preparations, potentiates C3b inactivation by C3b inactivator, binds EAC43 to limit EAC43bB/EAC43bBP formation, and accelerates loss of hemolytic sites, with first‑order kinetics requiring simultaneous presence of both proteins.

Abstract

C3b inactivator accelerator (A-C3bINA) was isolated from human plasma. An antiserum produced against the purified protein gave a reaction of identity with beta 1 H, a well-documented contaminant of C3 preparations. Beta 1 H appears to be composed of a single polypeptide chain containing a significant quantity of carbohydrate, and having a sedimentation coefficient of 5.6 on analytical, and 6.4 on sucrose density gradient ultracentrifugation. Its mol wt based on SDS polyacrylamide gel electrophoresis and equilibrium sedimentation is approximately 150,000, whereas it elutes from Sephadex G200 with an apparent mol wt of 300,000, suggesting that beta 1 H is an asymmetric molecule. Beta 1 H potentiates the inactivation of C3b by C3b inactivator, binds to EAC43 to limit the formation of EAC43bB and EAC43bBP, and in contrast to C3b inactivator, it increases the rate of loss of hemolytic sites from EAC43bB and EAC43bBP. For the C3b inactivator-potentiating effect, beta 1 H and C3b inactivator must necessarily be simultaneously present. The kinetics of inactivation of C3b by C3b inactivator and beta 1 H are first order, suggesting that potentiation is not a multistep process. The mechanisms of binding to C3b and inhibition of the alternative pathway convertases C3bB and C3bBP are currently unknown.