Modulation of the alternative complement pathway by β1H globulin*

Abstract

C3b inactivator accelerator (A. C3bINA) was isolated from human plasma. An antiserum produced against the purified protein gave a reaction of identity with β1H, a well-documented contaminant of C3 preparations, β1H 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 β1H is an asymmetric molecule. β1H potentiates the inactivation of C3b by C3b inactivator, binds to EAC43 to limit the formation of EAC43bB and EAC43BP, and in contrast to C3b inactivator, it increases the rate of loss of hemolytic sites from EAC433bB and EAC43bBP. For the C3b inactivator-potentiating effect, fllH and C3b inactivator must necessarily be simultaneously present. The kinetics of inactivation of C3b by C3b inactivator and fllH 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. © 1976, Rockefeller University Press., All rights reserved.