Efficacy of HIV‐specific and ‘antibody‐independent’ mechanisms for complement activation by HIV‐infected cells
Previous studies in this laboratory have shown that efficient activation of complement (C) on HIV isolates and HIV‐infected cells requires the binding of specific anti‐HIV antibodies, while other investigators have observed ‘antibody‐independent’ C activation. In an attempt to clarify these disparate findings, we investigated the effect of several variables on C activation by HIV‐infected cells using flow cytometric analysis of C3 deposition. Antibody‐mediated C activation using pooled sera from infected persons or human MoAbs directed against the V3 region of gp120 was always substantially higher than activation without antibody. Normal human serum (NHS) from a subset of HIV antibody‐negative donors did, however, induce low levels of C3 deposition. Differences in C3 activation between the various NHS did not correlate with total haemolytic C levels or mannose‐binding protein (MBP) levels. IgM isolated from NHS that induced high levels of C activation was at least partly responsible for the ‘antibody‐independent’ C activation. Although there appeared to be a correlation between NHS that induced C activation and the presence of anti‐blood type B IgM, absorption of anti‐B did not abrogate the C3 deposition. Additionally. MoAb to the B antigen did not induce C3 deposition. These studies show that IgM in sera from HIV‐uninfected donors can induce C3 deposition on HIV‐infected cells, but that specific antibody‐dependent C activation is substantially more efficient. Therefore,‘antibody‐independent’ C activation on HIV‐infected cells may, in some cases, be more accurately described as HIV‐cross‐reactive antibody‐dependent C activation.