title: Complement activation by cold agglutinins.
abstract: Purified monoclonal human IgM cold agglutinins (CA) of different specificities (anti-I, anti-i, anti-Pr) were investigated for their complement-activating capacity in a homologous system. Incubation of human RBC with excess of IgM CA in the cold, and subsequently with human serum at 37 degrees C, resulted in striking differences in hemolysis. Hemolysis did not correlate to the amount of antibodies bound to RBC at 4 or 20 degrees C. Despite the hemolytic inefficiency of anti-i and anti-Pr CA tested, C1 fixation and subsequent activation of the classical pathway of complement could be assessed in all cases. Absolute numbers of C3 molecules bound to RBC, exceeding the critical level to initiate the terminal sequence of the complement cascade, could not fully explain the differences in the hemolytic activity of the CA. Since C8 binding protein (C8bp) carries I determinants it is hypothesized that anti-I-induced complement-mediated hemolysis might also be favored by the binding of the autoantibody to and probably steric hindrance of this major regulatory protein of the terminal complement sequence. The prominent role of homologous restriction of complement-mediated lysis as a protective mechanism can also be deduced from the fact that rabbit as well as rat serum as a source of heterologous complement lysed cold agglutinin-sensitized red blood cells more efficiently than human serum.
authors.affiliation: Institute of Immunology, University of Heidelberg, FRG.
authors.forename: M
authors.initials: M
authors.lastname: Kirschfink
authors.forename: H
authors.initials: H
authors.lastname: Fritze
authors.forename: D
authors.initials: D
authors.lastname: Roelcke
mesh_terms: D000373:Agglutinins / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D003080:Cold Temperature; D003167:Complement Activation / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques
chemical_list: D000373:Agglutinins; D000911:Antibodies, Monoclonal; D001323:Autoantibodies