Leukocyte complement: a possible role for C5 in lymphocyte stimulation

The results presented here show that Fab' antibody fragments directed to complement proteins C5, C6, and C7 inhibit lymphocyte stimulation in mixed lymphocyte culture (MLC) by up to 65%, as determined by decreased incorporation of 3H-thymidine. Lymphocyte stimulation induced by PHA-mitogen was also inhibited up to 100% by anti-C5 Fab'. Specificity of these reactions was established by the findings that goat anti-C5 or murine hybridoma anti-C5 both inhibited MLC; the inhibitory activity of anti-C5 Fab' was absorbed with highly purified C5 (but not with C3), and antibody directed to C3 did not inhibit lymphocyte stimulation by MLC or PHA. The effects of anti-C5 were exerted in a nontoxic manner. Cleavage of lymphocyte associated C5 with factor B (Bb) or with trypsin resulted in stimulation of lymphocyte thymidine incorporation. Purified C5a was found to induce lymphocyte stimulation in serum-free medium in pulse-chase types of experiments. Anti-C6 and C7 Fab' also inhibited lymphocyte stimulation induced in one-way MLC. These results suggest that C5, C5a, and/or C6 and C7 may play a role in triggering of lymphocyte blastogenesis.