Biosynthesis of C4 by mouse peritoneal macrophages. I. Characterization of an in vitro culture system and comparison of C4 synthesis by "low" vs "high" C4 strains.

C4 biosynthesis and secretion in mouse resident peritoneal macrophage cultures was examined by functional and antigenic analysis. The rate of secretion of functional and antigenic C4 decreased in parallel in short-term culture despite constant total protein secretion and increasing factor B secretion. Feedback inhibition and protease degradation did not account for the decreasing rate of C4 secretion. Despite a 10-fold difference in plasma C4 levels between high C4 (H-2d haplotype) and low C4 (H-2k haplotype) mouse strains, resident peritoneal macrophages from both strains synthesized and secreted similar amounts of antigenic and functional C4 in short-term culture. The C4 secreted by H-2d and H-2k macrophages was relatively stable, because it exhibited only approximately 2% loss of hemolytic activity per hour in culture. These data suggest that an unidentified environmental signal leads to the specific decrease in C4 synthesis and secretion by peritoneal macrophages and that a regulatory defect may not be present, at least in macrophages, to account for the low C4 levels in the H-2k haplotype.