Complement-dependent B-cell activation by cobra venom factor and other mitogens?
It has been proposed that two distinct signals are required for the triggering of the precursors of antibody-forming bone marrow-derived cells (B cells): (a) the binding of antigen or of a mitogen to the corresponding receptor sites on B-cell membranes and (b) the interaction of activated C3 with the C3 receptor of B lymphocytes. There is growing evidence that B-cell mitogens and T (thymus-derived cell)-independent antigens are capable of activating the alternate pathway of the complement system (bypass). Therefore, the effect of another potent bypass inducer was investigated with regard to B-cell activation and the role of C3. Purified, pyrogen-free cobra venom factor was mitogenic for both T and B lymphocytes (cortisone-resistant mouse thymus cells and lymph node lymphocytes from congenitally athymic mice). Venom factor could substitute for T cells by restoring the potential of antibody formation to sheep red blood cells in mouse B-cell cultures supplemented with macrophages or 2-mercaptoethanol. Venom factor may be capable of conferring activated C3 to the C3 receptor of B lymphocytes: preincubation of lymphoid cells with homologous serum or plasma, 10 mM EDTA, and sepharose-coupled venom factor converted with serum to an enzyme active against C3, inhibited their capacity to subsequently form rosettes with sheep erythrocytes sensitized with amboceptor and C5-deficient mouse complement. In the absence of EDTA, preincubation of freshly prepared B-cell suspensions with C3-sufficient homologous serum also blocked their subsequent interaction with complement-sensitized erythrocytes and at the same time rendered them reactive to an otherwise T-cell-specific mitogen. Moreover, mitogen induced B-cell proliferation in lymph node (but not in spleen) cell cultures, appeared to depend on the availability of exogenous C3: zymosan-absorbed fetal bovine serum (only 8.3% site-forming units remaining) supported T-cell activation by phytohemagglutinin, concanavalin A, and venom factor, but failed to sustain B-cell stimulation by pokeweed mitogen, lipopolysaccharide, and venom factor. T-cell-dependent antibody formation in composite cultures containing T cells or T-cell-substituting B-cell mitogens, B cells, and macrophages, always required the presence of C3-sufficient serum.
D000818:Animals; D000917:Antibody Formation; D000942:Antigens, Bacterial; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003165:Complement System Proteins; D003208:Concanavalin A; D004912:Erythrocytes / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D006462:Hemolytic Plaque Technique; D007104:Immune Adherence Reaction; D007700:Kinetics; D037102:Lectins; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008934:Mitogens; D011134:Polysaccharides; D012756:Sheep / Q000276:immunology; D012911:Snakes; D013601:T-Lymphocytes / Q000276:immunology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014688:Venoms
D000942:Antigens, Bacterial; D037102:Lectins; D008070:Lipopolysaccharides; D008934:Mitogens; D011134:Polysaccharides; D014688:Venoms; D014316:Tritium; D003208:Concanavalin A; D003165:Complement System Proteins; D013936:Thymidine