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

Abstract

C3b [b fragment of the 3rd complement component] inactivator accelerator (A .cntdot. C3bINA) was isolated from human plasma. An antiserum produced against the purified protein gave a reaction of identity with .beta.1H, a well-documented contaminant of C3 preparations. .beta.1H 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 MW based on SDS polyacrylamide gel electrophoresis and equilibrium sedimentation is approximately 150,000, whereas, it elutes from Sephadex G200 with an apparent MW of 300,000, suggesting that .beta.1H is an asymmetric molecule. .beta.1H potentiates the inactivation of C3b by C3b inactivator, binds to EAC43 [sheep erythrocyte, rabbit antibody, C4 plus C3 complex] to limit the formation of .**GRAPHIC**. [E, A plus activated C4, C3b, factor B complex] and .**GRAPHIC**. plus activated properdin complex], and in contrast to C3b inactivator, it increases the rate of loss of hemolytic sites from .**GRAPHIC**. and .**GRAPHIC**. For the C3b inactivator-potentiating effect, .beta.1H and C3b inactivator must necessarily be simultaneously present. The kinetics of inactivation of C3b by C3b inactivator and .beta.1H are 1st order, suggesting that potentiation is not a multistep process. The mechanisms of binding to C3b and inhibition of the alternative pathway convertases .**GRAPHIC**. and .**GRAPHIC**. are currently unknown.