Role of complement component C1q in the IgG-independent opsonophagocytosisof group B Streptococcus

We investigated the role of complement component C1q in the IgG-independent opsonophagocytosis of type III group B Streptococcus (GBS) by peripheral b lood leukocytes, We report that C1q binds to type III GBS both in normal hu man serum deficient in IgG specific for type III capsular polysaccharide an d: in a low-ionic strength buffer. The dissociation constant K-d ranged fro m 2.0 to 5.5 nM, and the number of binding sites B-max ranged from 630 to 1 360 molecules of C1q per bacterium (CFU), An acapsular mutant strain of GBS bound C1q even better than the wild type, indicating that the polysacchari de capsule is not the receptor for C1q, In serum, binding of C1q to GBS was associated with activation of the classical complement pathway. However, n ormal human serum retained significant opsonic activity after complete depl etion of C1q, suggesting that the serum contains a molecule that is able to replace C1q in opsonization and/or complement activation, Mannan-binding l ectin, known to share some functions with C1q, appeared not to be involved, since its depletion from serum had little effect on opsonic activity. Exce ss soluble C1q or its collagen-like fragment inhibited phagocytosis mediate d by normal human serum, suggesting that C1q may compete with other opsonin s for binding to receptor(s) on phagocytes,We conclude that, although C1q b inds directly to GBS, C1q binding is neither necessary nor sufficient for I gG-independent opsonophagocytosis. The results raise the possibility that a dditional unknown serum factor(s) may contribute to opsonization of GBS dir ectly car via a novel mechanism of complement activation.