C1q inhibitor (C1qINH): Functional properties and possible relationship to a lymphocyte membrane-associated C1q precipitin

A serum inhibitor of C1q (C1qINH) was isolated and its functional properties were studied. C1qINH was found to abrogate the C1q hemolytic activity in a dose-dependent fashion requiring an incubation period of 20 min for optimal inhibition. Quantitative precipitin studies showed that C1q inhibitor binds to and precipitates isolated C1q forming a C1q-C1qINH complex with a peak of precipitation at the zone of equivalence. Preincubation of NHS containing 0.01 M EDTA with C1qINH resulted in a marked decrease (60%) when the mixture was tested for hemolytic activity in the presence of calcium. However, no effect was observed when the inhibitor was preincubated with NHS without EDTA, suggesting that C1qINH binds to free C1q in serum but not when it is in complex with C1r and C1s. The uptake of ¹²⁵IC1q by lymphocytes was also abrogated when the C1q was first preincubated with the inhibitor. Since C1q binds to lymphocyte receptors and to the C1r-Ca⁺⁺-C1s complex by its collagenous tail, it is inferred that C1q inhibitor may also bind to the collagenous portion of C1q, thereby abrogating its capacity to initiate the complement cascade and attach to C1q receptors on lymphocytes. In addition, an activity that is inhibitory to the C1q-dependent biologic functions was solubilized from the membranes of peripheral blood lymphocytes. The membrane-associated material was found to abrogate C1q hemolytic activity, to bind free C1q in EDTA-treated serum, and to precipitate isolated C1q when analyzed by double immunodiffusion techniques. These results demonstrate that the serum C1qINH can control C1q-dependent immune reactions and tend to suggest that C1qINH might be identical with or related to the inhibitor isolated from lymphocyte membranes. This could mean that C1qINH might be synthesized by lymphocytes and carried as a C1q receptor, which is partly shed into the blood stream as new receptors are synthesized.