Molecular composition of complement-solubilized complexes and their fate in vivo

Radiolabelled bovine serum albumin (BSA)-rabbit anti-BSA complexes formed at equivalence were solubilized by fresh human sera as a source of complement and analysed in 10-50% w/w sucrose density gradients. The solubilized complexes were heterogeneous, having sizes ranging from 9 to 25 S. The profiles of antigen and antibody in the complexes matched each other, indicating that solubilization is not due to dissociation of antigen-antibody bonds. The complexes could be precipitated from solution by specific antisera to C3 or C3c, but not to C1q, C4 or rabbit Fc. Although insoluble precipitates could be solubilized via the alternative pathway alone, the process was more rapid when the classical pathway was also available. Unlike the complexes which had not been solubilized by complement, a small fraction of the latter could not be dissociated at low pH(2.8) or by cationic detergent, and appeared to be covalently held together. Large aggregates of heated IgG could also be solubilized. In this case the process depended largely or solely on the classical pathway. The fate of labelled solubilized complexes was studied after i.v. injection into C3H/He mice. Clearance from the blood was slower and uptake by liver and lung was diminished compared with insoluble complexes. Solubilized complexes were preferentially taken up and retained in germinal centres of the spleen. This may be important for the generation of B-memory cells.