Interaction of C1q with its receptor on cultured cell lines induces an anti-proliferative response

Abstract The receptor for human C1q (C1qR) is expressed on a wide variety of somatic cells, including cultured cell lines of different lineages such as Raji, Daudi, Wil 2 WT, U937, and Molt 4 . In this report, we present evidence which shows that culturing of C1qR-expressing cell lines with C1q inhibits their growth. When each of the different cell lines were cultured for 5 days with or without various concentrations (5–50 μg/ml) of microfiltered (0.22 μm) C1q, cell proliferation was inhibited in a dose-dependent manner with maximal inhibition (90%) occurring at a concentration of 50 μg/ml at Day 4 of culture. This anti-proliferative effect of C1q was inhibited when 30 μg/ml of F(ab′) 2 anti-C1q was included in the culture with C1q while the antibody alone did not have any effect. The specificity of this interaction was further substantiated by the finding that neither macromolecular C1, or subcomponents C1r and C1s, nor human or murine IgG nor IgM had any inhibitory activity when cultured with these cell lines. That this C1q-induced inhibition of cell growth is mediated by C1qR was deduced from experiments in which (i) culturing of cells in the presence of two IgM monoclonal antibodies II1/D1 and II1/B5, directed against the C1q-binding site of C1qR resulted in the inhibition of cell growth while nonimmune murine IgM did not, and (ii) the collagenous portion of C1q (c-C1q) which contains the intact, C1qR-binding domain was also capable of inhibiting cell proliferation in a manner similar to intact C1q. The effect of C1q was not cytotoxic but cytostatic since the number of dead cells in the C1q-treated cultures was not significantly different than that in the untreated cells (5% vs 4%), a figure which represents the normal wear and tear of tissue culture conditions. On the basis of these findings we propose that the C1qR alone or in conjunction with other cellular factors may function as a molecule which supports cell growth. Upon ligand binding, however, the ligand-receptor interaction may suppress postreceptor events which are necessary for cell proliferation.