Effects of anti-C4 antibody on complement production by splenic and peritoneal macrophages.

We have previously shown that administration of anti-C4 antibody to cells in culture can suppress the synthesis and secretion of C4. Lymphoid cells must be present along with the C4 secreting macrophages to achieve suppression of full magnitude and long duration. In this publication we have demonstrated that treatment of peritoneal macrophages with intact anti-C4 antibody results in reduction of intracellular and secreted C4. Intracellular levels of pro-C4 rapidly returned to normal after removal of the suppressing antibody and extracellular levels of C4 secreted into the media returned to normal within 24-48 h. This is in marked contrast to our previously published results with splenic fragments where intracellular pro-C4 remained markedly reduced long after removal of anti-C4. Using pulse-chase experiments we now demonstrate that, after recovery from suppression, intracellular pro-C4 levels remain low in splenic macrophages because nascent C4 is processed through the cell more rapidly. This results in a smaller intracellular pool of C4, even in the face of normal or high levels of C4 synthesis in the postsuppression phase. Finally, we demonstrate that suppression of full magnitude and duration could only be achieved with intact anti-C4 antibody. F(ab')2 fragments were not capable of inducing complete suppression.